Advanced Solid TumorsPhase 1/2NCT01693562
A Phase 1/2 Study to Evaluate MEDI4736
A Phase 1/2 study testing MEDI4736 in people with Advanced Solid Tumors, run by MedImmune LLC at 79 sites in 9 countries.
Trial summary
This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in participants with advanced solid tumors followed by an expansion phase in participants with advanced solid tumors. An exploration cohort has been added to determine the safety using every 4 weeks (Q4W) dosing. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- MEDI4736
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,022 participants
- Where
- 79 sitesin 9 countries
- Study dates
- 5 Sep 2012to 28 Feb 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 or older.
- In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.
- In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, participants must have failed, be intolerant to, be ineligible for, or have refused
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
- Adequate organ and marrow function.
- Participants must have at least 1 measurable lesion.
- Available archived tumor tissue sample.
- Willingness to provide consent for biopsy sample (dose-expansion only)
Who cannot join
- Any prior Grade ≥ 3 immune-mediated adverse event (imAE) while receiving immunotherapy
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
- Prior treatment with immunotherapy agents including, but not limited to, tumor necrosis factor receptor superfamily agonists or checkpoint inhibitors or natural killer (NK) cell inhibitors.
- Active or prior documented autoimmune disease within the past 2 years
- History of primary immunodeficiency
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- History of organ transplant that requires use of immunosuppressives
- Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment
- Other invasive malignancy within 2 years
- Women who are pregnant or lactating
- Uncontrolled intercurrent illness
- Known history of tuberculosis
- Known to be human immunodeficiency virus (HIV) positive
- Known to be Hepatitis B or C positive (except HCC participants)
Trial locations and contacts
79 sites in 9 countries.
79 sites in 9 countries
United States47 sites
Research Site
Ann Arbor, Michigan, 48109
Research Site
Athens, Georgia, 30607
Research Site
Augusta, Georgia, 30912
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Baltimore, Maryland, 21201
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Baltimore, Maryland, 21231
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Billings, Montana, 59101
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Blacksburg, Virginia, 24060
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Boston, Massachusetts, 02215
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Burbank, California, 91505
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Chapel Hill, North Carolina, 27599
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Chicago, Illinois, 60637
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Cleveland, Ohio, 44106
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Columbus, Ohio, 43210
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Dallas, Texas, 75201
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Detroit, Michigan, 48201
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Fairfax, Virginia, 22031
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Gilroy, California, 95020
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Greenville, South Carolina, 29605
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Hackensack, New Jersey, 07601
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Houston, Texas, 77030
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Houston, Texas, 77090
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Huntersville, North Carolina, 28078
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Jacksonville, Florida, 32224
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Las Vegas, Nevada, 89169
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Los Angeles, California, 90025
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Los Angeles, California, 90095
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Miami Beach, Florida, 33140
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Minneapolis, Minnesota, 55407
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Nashville, Tennessee, 37203
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New Haven, Connecticut, 06520
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New York, New York, 10065
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Orange, California, 92868
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Palo Alto, California, 94304-5826
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Paterson, New Jersey, 07503
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Philadelphia, Pennsylvania, 19107-5097
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Pittsburgh, Pennsylvania, 15212
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Portland, Oregon, 97213
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Saint Louis Park, Minnesota, 55416
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Salt Lake City, Utah, 84403
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San Antonio, Texas, 78229
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San Francisco, California, 94115
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Scottsdale, Arizona, 85258
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Seattle, Washington, 98104
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Tampa, Florida, 33612
Research Site
The Bronx, New York, 10461
Research Site
Washington D.C., District of Columbia, 20007
Research Site
Whittier, California, 90603
South Korea6 sites
Research Site
Gwangju, 61469
Research Site
Seogu, 49241
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Germany5 sites
Research Site
Berlin, 12200
Research Site
Gauting, 82131
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Heidelberg, 69120
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Jena, 07747
Research Site
Minden, 32429
Italy5 sites
Research Site
Lecce, 73100
Research Site
Milan, 20141
Research Site
Milan, 20132
Research Site
Naples, 80131
Research Site
Siena, 53100
United Kingdom5 sites
Research Site
London, EC1A 7BE
Research Site
London, SW2 6JJ
Research Site
London, W1G 6AD
Research Site
Oxford, OX3 7LE
Research Site
Sutton, SM2 5PT
Belgium4 sites
Research Site
Ghent, 9000
Research Site
Leuven, 3000
Research Site
Liège, B-4000
Research Site
Namur, 5000
Canada3 sites
Research Site
Montreal, Quebec, H2X 3E4
Research Site
Ottawa, Ontario, K1H 8L6
Research Site
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI4736 in Subjects With Advanced Solid Tumors
This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in participants with advanced solid tumors followed by an expansion phase in participants with advanced solid tumors. An exploration cohort has been added to determine the safety using every 4 weeks (Q4W) dosing.
Read the detailed description
A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death ligand-1 (PD-L1)) will evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity (IM), and antitumor activity of MEDI4736 in adult participants with solid tumors. A dose exploration cohort will look at the safety profile of Q4W dosing of MEDI4736.
- Conditions
- Advanced Solid Tumors
- Being tested
- MEDI4736
- Keywords
- Advanced solid tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI4736Drug
Also called Durvalumab
Participants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
| Study group | Role | What they receive |
|---|---|---|
| Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) | Experimental | Participants will receive intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) | Experimental | Participants will receive IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Escalation Cohort (MEDI4736 1 mg/kg Q2W) | Experimental | Participants will receive IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Escalation Cohort (MEDI4736 3 mg/kg Q2W) | Experimental | Participants will receive IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Escalation Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Escalation Cohort (MEDI4736 15 mg/kg Q3W) | Experimental | Participants will receive IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Exploration Durvalumab 20 mg/kg (Q4W) | Experimental | Participants will receive IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion Non-SCCHN Cohort HPV positive (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with non-small-cell lung cancer (NSCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with hepatocellular carcinoma (HCC Total) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with advance cutaneous melanoma (ACM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with uveal melanoma (UM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with gastroesophageal cancer (GEC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with triple-negative breast cancer (TNBC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with pancreatic adenocarcinoma (PAC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with urothelial carcinoma (UC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with glioblastoma multiforme (GBM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with ovarian cancer (OC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with soft- tissue sarcoma (STS) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with small-cell lung cancer (SCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with microsatellite instability (MSI)-high cancer will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
| Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Participants with nasopharyngeal carcinoma (NPC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: MEDI4736 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase
A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period including any >= Grade 3 colitis or >= Grade 3 immune-related adverse event (irAE; AEs of immune nature in the absence of a clear alternative etiology) including rash, pruritus, or diarrhea that did not downgrade to =< Grade 2 within 3 days after onset of the event despite maximal supportive care including systemic corticosteroids. The DLT-evaluation period for 0.1 to 10 mg/kg arms was from Day 1 to Day 28 of first dose and for 15 mg/kg arm was from Day 1 to Day 42 of first dose.
Measured: For MEDI4736 0.1 to MEDI4736 10 mg/kg arms: from Day 1 to Day 28 of first dose; for MEDI4736 15 mg/kg arm: from Day 1 to Day 42 of first dose
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Measured: From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of coagulation, urine, hematology, and serum chemistry.
Measured: From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
Number of Participants With Abnormal Vital Signs Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body weight, body temperature, blood pressure, pulse rate, and respiratory rate).
Measured: From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
Number of Participants With Change From Baseline in QT/QTc Interval in Local Electrocardiogram in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
Number of participants with change from baseline in notable QT/QTc interval in local electrocardiogram (ECG) are reported. The data for >0 participants with notable QT/QTc interval in local ECG from baseline are reported.
Measured: From Baseline (Day 1) through 90 days after the last dose of study drug (approximately 5.25 years)
Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) in Participants With Non-squamous NSCLC Who Had Received 2 or More Prior Lines of Therapy in the Dose-expansion Phase
The ORR assessed by BICR in participants with non-squamous NSCLC who had received 2 or more prior lines of therapy is reported. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
ORR Assessed by BICR in Participants With Squamous NSCLC Who Had Received 1 and 2 or More Prior Lines of Therapy in the Dose-expansion Phase
The ORR assessed by BICR in participants with squamous NSCLC who had received 1 and 2 or more prior lines of therapy is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
ORR Assessed by BICR in Participants With UC Post-platinum (Programmed Cell Death Ligand [PD-L1] Status High) Who Had Received at Least 1 Line of Prior Therapy (2L+) in the Dose-expansion Phase
The ORR assessed by BICR in participants with UC post-platinum PD-L1 status high 2L+ is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Secondary outcomes (24)
Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase
Area under the concentration-time curve from time zero to the last measurable concentration (AUClast) of MEDI4736 is reported.
Measured: After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)
Maximum Serum Concentration (Cmax) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase
The Cmax of MEDI4736 is reported.
Measured: After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 in the Dose-escalation, Dose-exploration Phase, and Dose-expansion Phase.
Number of participants with positive ADA titer to MEDI4736 are reported. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration; persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment; and transient positive is defined as having at least one post-baseline ADA-positive assessment and not fulfilling the condition of persistent positive.
Measured: Escalation: Day1 of Dose(D)1 & D3, even numbered doses after D4; Exploration: Day1 of D1 & D2, even numbered doses after D2; Expansion: Day1 of D1, every 12 weeks since D3; all phases: till EOT, 30 days and 3 and 6 months post last dose (~5.25 years)
Number of Participants With Best Overall Response (BOR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase
The BOR assessed by BICR based on RECIST v1.1 in NSCLC and SCCHN cohorts is reported. The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE). The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Number of Participants With BOR Assessed by Investigator in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
The BOR assessed by investigator based on RECIST v1.1 is reported. The BOR includes CR, PR, SD, PD, and NE. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Duration of Response (DoR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase
The DoR assessed by BICR in NSCLC and SCCHN cohorts is reported. The DoR is defined as the duration from the first documentation of objective response (OR) (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DoR Assessed by Investigator in the Dose-expansion Phase
The DoR in participants assessed by the investigator is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Disease Control Rate (DCR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase
Percentage of participants with disease control assessed by BICR in NSCLC and SCCHN cohorts is reported. Disease control is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DCR Assessed by Investigator in the Dose-expansion Phase
Percentage of participants with disease control assessed by the investigator is reported. Disease control is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Progression-free Survival (PFS) Assessed by BICR in NSCLC Cohort in the Dose-expansion Phase
The PFS assessed by BICR in NSCLC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
PFS Assessed by BICR in SCCHN Cohort in the Dose-expansion Phase
The PFS assessed by BICR in SCCHN cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
PFS Assessed by Investigator in the Dose-expansion Phase
The PFS assessed by the investigator is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
OS in the Dose-Expansion Phase
OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
ORR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
The ORR assessed by BICR in UC cohort is reported. The ORR is defined as confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
ORR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
The ORR assessed by the investigator in UC cohort is reported. The ORR is defined as confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DoR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
The DoR assessed by BICR in UC cohort is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DoR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
The DoR assessed by investigator in UC cohort is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DCR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Percentage of participants with disease control assessed by BICR in UC cohort is reported. The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DCR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Percentage of participants with disease control assessed by investigator in UC cohort is reported. Disease control is defined as a best overall response of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 28 days with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR not sufficient increase to qualify for disease progression.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
PFS Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
The PFS assessed by BICR in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
PFS Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
The PFS assessed by the investigator in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
OS in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
The OS in UC cohort is reported. The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Adjusted Comparison of PFS by PD-L1 Status in UC Cohort in the Dose-expansion Phase
The PFS by PD-L1 status in UC cohort is reported. The PFS estimates are adjusted for baseline eastern cooperative oncology (ECOG), smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Adjusted Comparison of OS by PD-L1 Status in UC Cohort in the Dose-expansion Phase
The OS by PD-L1 status in UC cohort is reported. The OS estimates are adjusted for baseline ECOG, smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method.
Measured: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2012 (estimated)
- Study start5 Sep 2012
- Primary completion28 Feb 2020
- Study completion28 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1,022 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MedImmune, LLC, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01693562
- Sponsor's protocol ID
- CD-ON-MEDI4736-1108
- Status last verified
- Apr 2021
- First submitted
- 14 Sep 2012
- Last updated
- 13 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Li Q, Cristini V, Gupta A, Achour I, Barrett JC, Koay EJ. Clinical Validation of Mathematically Derived Early Tumor Dynamics for Solid Tumors in Response to Durvalumab. JCO Clin Cancer Inform. 2024 Jul;8:e2300254. doi: 10.1200/CCI.23.00254.
PubMed 38996196Gavrilov S, Zhudenkov K, Helmlinger G, Dunyak J, Peskov K, Aksenov S. Longitudinal Tumor Size and Neutrophil-to-Lymphocyte Ratio Are Prognostic Biomarkers for Overall Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Durvalumab. CPT Pharmacometrics Syst Pharmacol. 2021 Jan;10(1):67-74. doi: 10.1002/psp4.12578. Epub 2020 Dec 21.
PubMed 33319498Sheth S, Gao C, Mueller N, Angra N, Gupta A, Germa C, Martinez P, Soria JC. Durvalumab activity in previously treated patients who stopped durvalumab without disease progression. J Immunother Cancer. 2020 Aug;8(2):e000650. doi: 10.1136/jitc-2020-000650.
PubMed 32847985Zhang Q, Luo J, Wu S, Si H, Gao C, Xu W, Abdullah SE, Higgs BW, Dennis PA, van der Heijden MS, Segal NH, Chaft JE, Hembrough T, Barrett JC, Hellmann MD. Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade. Cancer Discov. 2020 Dec;10(12):1842-1853. doi: 10.1158/2159-8290.CD-20-0047. Epub 2020 Aug 14.
PubMed 32816849Zajac M, Ye J, Mukhopadhyay P, Jin X, Ben Y, Antal J, Gupta AK, Rebelatto MC, Williams JA, Walker J. Optimal PD-L1-high cutoff for association with overall survival in patients with urothelial cancer treated with durvalumab monotherapy. PLoS One. 2020 Apr 27;15(4):e0231936. doi: 10.1371/journal.pone.0231936. eCollection 2020.
PubMed 32339189Nordstrom BL, Oguz M, Chu BC, Ouwens M, Arkenau HT, Klein AB. Effectiveness of durvalumab versus chemotherapy in metastatic urothelial cancer: an observational, indirect comparison. J Comp Eff Res. 2020 Feb;9(3):191-199. doi: 10.2217/cer-2019-0163. Epub 2020 Jan 9.
PubMed 31916448Antonia SJ, Balmanoukian A, Brahmer J, Ou SI, Hellmann MD, Kim SW, Ahn MJ, Kim DW, Gutierrez M, Liu SV, Schoffski P, Jager D, Jamal R, Jerusalem G, Lutzky J, Nemunaitis J, Calabro L, Weiss J, Gadgeel S, Bhosle J, Ascierto PA, Rebelatto MC, Narwal R, Liang M, Xiao F, Antal J, Abdullah S, Angra N, Gupta AK, Khleif SN, Segal NH. Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC. J Thorac Oncol. 2019 Oct;14(10):1794-1806. doi: 10.1016/j.jtho.2019.06.010. Epub 2019 Jun 20.
PubMed 31228626Althammer S, Tan TH, Spitzmuller A, Rognoni L, Wiestler T, Herz T, Widmaier M, Rebelatto MC, Kaplon H, Damotte D, Alifano M, Hammond SA, Dieu-Nosjean MC, Ranade K, Schmidt G, Higgs BW, Steele KE. Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy. J Immunother Cancer. 2019 May 6;7(1):121. doi: 10.1186/s40425-019-0589-x.
PubMed 31060602Segal NH, Ou SI, Balmanoukian A, Fury MG, Massarelli E, Brahmer JR, Weiss J, Schoffski P, Antonia SJ, Massard C, Zandberg DP, Khleif SN, Xiao F, Rebelatto MC, Steele KE, Robbins PB, Angra N, Song X, Abdullah S, Butler M. Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. Eur J Cancer. 2019 Mar;109:154-161. doi: 10.1016/j.ejca.2018.12.029. Epub 2019 Feb 4.
PubMed 30731276Zajac M, Boothman AM, Ben Y, Gupta A, Jin X, Mistry A, Sabalos C, Nielsen A, Manriquez G, Barker C, Antal J, Wang P, Patil P, Schechter N, Rebelatto MC, Walker J. Analytical Validation and Clinical Utility of an Immunohistochemical Programmed Death Ligand-1 Diagnostic Assay and Combined Tumor and Immune Cell Scoring Algorithm for Durvalumab in Urothelial Carcinoma. Arch Pathol Lab Med. 2019 Jun;143(6):722-731. doi: 10.5858/arpa.2017-0555-OA. Epub 2018 Nov 20.
PubMed 30457897Steele KE, Tan TH, Korn R, Dacosta K, Brown C, Kuziora M, Zimmermann J, Laffin B, Widmaier M, Rognoni L, Cardenes R, Schneider K, Boutrin A, Martin P, Zha J, Wiestler T. Measuring multiple parameters of CD8+ tumor-infiltrating lymphocytes in human cancers by image analysis. J Immunother Cancer. 2018 Mar 6;6(1):20. doi: 10.1186/s40425-018-0326-x.
PubMed 29510739Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411. doi: 10.1001/jamaoncol.2017.2411. Epub 2017 Sep 14.
PubMed 28817753Levy A, Massard C, Soria JC, Deutsch E. Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. Eur J Cancer. 2016 Nov;68:156-162. doi: 10.1016/j.ejca.2016.09.013. Epub 2016 Oct 17.
PubMed 27764686
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI4736 in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01693562
- Acronym / sponsor ID
- CD-ON-MEDI4736-1108
- Conditions
- Advanced Solid Tumors
- Keywords
- Advanced solid tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,022 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 5 Sep 2012 (actual)
- Primary completion
- 28 Feb 2020 (actual)
- Study completion
- 28 Feb 2020 (actual)
- First posted
- 26 Sep 2012 (estimated)
- Results
- Posted 13 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in participants with advanced solid tumors followed by an expansion phase in participants with advanced solid tumors. An exploration cohort has been added to determine the safety using every 4 weeks (Q4W) dosing.
Detailed description
A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death ligand-1 (PD-L1)) will evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity (IM), and antitumor activity of MEDI4736 in adult participants with solid tumors. A dose exploration cohort will look at the safety profile of Q4W dosing of MEDI4736.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 23
| Arm | Type | Receives |
|---|---|---|
| Escalation Cohort (MEDI4736 0.1 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants will receive intravenous (IV) infusion of MEDI4736 (durvalumab) 0.1 mg/kg every 2 weeks (Q2W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Escalation Cohort (MEDI4736 0.3 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants will receive IV infusion of MEDI4736 0.3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Escalation Cohort (MEDI4736 1 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants will receive IV infusion of MEDI4736 1 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Escalation Cohort (MEDI4736 3 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants will receive IV infusion of MEDI4736 3 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Escalation Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Escalation Cohort (MEDI4736 15 mg/kg Q3W) | Experimental | Drug: MEDI4736Participants will receive IV infusion of MEDI4736 15 mg/kg every 3 weeks (Q3W) in the dose-escalation phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Exploration Durvalumab 20 mg/kg (Q4W) | Experimental | Drug: MEDI4736Participants will receive IV infusion of MEDI4736 20 mg/kg every 4 weeks (Q4W) in the dose-exploration phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion Non-SCCHN Cohort HPV positive (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with non-SCCHN human papilloma virus positive (Non-SCCHN HPV+) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with non-small-cell lung cancer (NSCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with hepatocellular carcinoma (HCC Total) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with advance cutaneous melanoma (ACM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion UM Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with uveal melanoma (UM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with gastroesophageal cancer (GEC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with triple-negative breast cancer (TNBC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with pancreatic adenocarcinoma (PAC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion UC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with urothelial carcinoma (UC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with glioblastoma multiforme (GBM) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion OC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with ovarian cancer (OC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion STS Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with soft- tissue sarcoma (STS) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with small-cell lung cancer (SCLC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with microsatellite instability (MSI)-high cancer will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose-expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W) | Experimental | Drug: MEDI4736Participants with nasopharyngeal carcinoma (NPC) will receive IV infusion of MEDI4736 10 mg/kg Q2W in the dose- expansion phase for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 or older.
- In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.
- In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, participants must have failed, be intolerant to, be ineligible for, or have refused
- Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
- Adequate organ and marrow function.
Key exclusion criteria (14 listed)
- Any prior Grade ≥ 3 immune-mediated adverse event (imAE) while receiving immunotherapy
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
- Prior treatment with immunotherapy agents including, but not limited to, tumor necrosis factor receptor superfamily agonists or checkpoint inhibitors or natural killer (NK) cell inhibitors.
- Active or prior documented autoimmune disease within the past 2 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI4736Also: DurvalumabParticipants will receive IV infusion of MEDI4736 for maximum of 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. | Drug | Escalation Cohort (MEDI4736 0.1 mg/kg Q2W), Escalation Cohort (MEDI4736 0.3 mg/kg Q2W), Escalation Cohort (MEDI4736 1 mg/kg Q2W), Escalation Cohort (MEDI4736 10 mg/kg Q2W), Escalation Cohort (MEDI4736 15 mg/kg Q3W), Escalation Cohort (MEDI4736 3 mg/kg Q2W), Expansion ACM Cohort (MEDI4736 10 mg/kg Q2W), Expansion GBM Cohort (MEDI4736 10 mg/kg Q2W), Expansion GEC Cohort (MEDI4736 10 mg/kg Q2W), Expansion HCC Total Cohort (MEDI4736 10 mg/kg Q2W), Expansion MSI-high Cancer Cohort (MEDI4736 10 mg/kg Q2W), Expansion NPC Cohort (MEDI4736 10 mg/kg Q2W), Expansion NSCLC Cohort (MEDI4736 10 mg/kg Q2W), Expansion Non-SCCHN Cohort HPV positive (MEDI4736 10 mg/kg Q2W), Expansion OC Cohort (MEDI4736 10 mg/kg Q2W), Expansion PAC Cohort (MEDI4736 10 mg/kg Q2W), Expansion SCCHN Cohort (MEDI4736 10 mg/kg Q2W), Expansion SCLC Cohort (MEDI4736 10 mg/kg Q2W), Expansion STS Cohort (MEDI4736 10 mg/kg Q2W), Expansion TNBC Cohort (MEDI4736 10 mg/kg Q2W), Expansion UC Cohort (MEDI4736 10 mg/kg Q2W), Expansion UM Cohort (MEDI4736 10 mg/kg Q2W), Exploration Durvalumab 20 mg/kg (Q4W) |
Primary outcome
Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase
Time frame: For MEDI4736 0.1 to MEDI4736 10 mg/kg arms: from Day 1 to Day 28 of first dose; for MEDI4736 15 mg/kg arm: from Day 1 to Day 42 of first dose
A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period including any >= Grade 3 colitis or >= Grade 3 immune-related adverse event (irAE; AEs of immune nature in the absence of a clear alternative etiology) including rash, pruritus, or diarrhea that did not downgrade to =< Grade 2 within 3 days after onset of the event despite maximal supportive care including systemic corticosteroids. The DLT-evaluation period for 0.1 to 10 mg/kg arms was from Day 1 to Day 28 of first dose and for 15 mg/kg arm was from Day 1 to Day 42 of first dose.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
Time frame: From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
Time frame: From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of coagulation, urine, hematology, and serum chemistry.
Number of Participants With Abnormal Vital Signs Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
Time frame: From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years)
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body weight, body temperature, blood pressure, pulse rate, and respiratory rate).
Number of Participants With Change From Baseline in QT/QTc Interval in Local Electrocardiogram in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
Time frame: From Baseline (Day 1) through 90 days after the last dose of study drug (approximately 5.25 years)
Number of participants with change from baseline in notable QT/QTc interval in local electrocardiogram (ECG) are reported. The data for >0 participants with notable QT/QTc interval in local ECG from baseline are reported.
Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) in Participants With Non-squamous NSCLC Who Had Received 2 or More Prior Lines of Therapy in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
The ORR assessed by BICR in participants with non-squamous NSCLC who had received 2 or more prior lines of therapy is reported. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
ORR Assessed by BICR in Participants With Squamous NSCLC Who Had Received 1 and 2 or More Prior Lines of Therapy in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
The ORR assessed by BICR in participants with squamous NSCLC who had received 1 and 2 or more prior lines of therapy is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
ORR Assessed by BICR in Participants With UC Post-platinum (Programmed Cell Death Ligand [PD-L1] Status High) Who Had Received at Least 1 Line of Prior Therapy (2L+) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
The ORR assessed by BICR in participants with UC post-platinum PD-L1 status high 2L+ is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between.
24 secondary outcomes
Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase
Time frame: After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)
Maximum Serum Concentration (Cmax) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase
Time frame: After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg)
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 in the Dose-escalation, Dose-exploration Phase, and Dose-expansion Phase.
Time frame: Escalation: Day1 of Dose(D)1 & D3, even numbered doses after D4; Exploration: Day1 of D1 & D2, even numbered doses after D2; Expansion: Day1 of D1, every 12 weeks since D3; all phases: till EOT, 30 days and 3 and 6 months post last dose (~5.25 years)
Number of Participants With Best Overall Response (BOR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Number of Participants With BOR Assessed by Investigator in the Dose-escalation, Dose-exploration, and Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Duration of Response (DoR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DoR Assessed by Investigator in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Disease Control Rate (DCR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DCR Assessed by Investigator in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Progression-free Survival (PFS) Assessed by BICR in NSCLC Cohort in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
PFS Assessed by BICR in SCCHN Cohort in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
PFS Assessed by Investigator in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
OS in the Dose-Expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
ORR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
ORR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DoR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DoR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DCR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
DCR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
PFS Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
PFS Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
OS in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Adjusted Comparison of PFS by PD-L1 Status in UC Cohort in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Adjusted Comparison of OS by PD-L1 Status in UC Cohort in the Dose-expansion Phase
Time frame: From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38996196Li Q, Cristini V, Gupta A, Achour I, Barrett JC, Koay EJ. Clinical Validation of Mathematically Derived Early Tumor Dynamics for Solid Tumors in Response to Durvalumab. JCO Clin Cancer Inform. 2024 Jul;8:e2300254. doi: 10.1200/CCI.23.00254.
- Derived from this study: PubMed 33319498Gavrilov S, Zhudenkov K, Helmlinger G, Dunyak J, Peskov K, Aksenov S. Longitudinal Tumor Size and Neutrophil-to-Lymphocyte Ratio Are Prognostic Biomarkers for Overall Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Durvalumab. CPT Pharmacometrics Syst Pharmacol. 2021 Jan;10(1):67-74. doi: 10.1002/psp4.12578. Epub 2020 Dec 21.
- Derived from this study: PubMed 32847985Sheth S, Gao C, Mueller N, Angra N, Gupta A, Germa C, Martinez P, Soria JC. Durvalumab activity in previously treated patients who stopped durvalumab without disease progression. J Immunother Cancer. 2020 Aug;8(2):e000650. doi: 10.1136/jitc-2020-000650.
- Derived from this study: PubMed 32816849Zhang Q, Luo J, Wu S, Si H, Gao C, Xu W, Abdullah SE, Higgs BW, Dennis PA, van der Heijden MS, Segal NH, Chaft JE, Hembrough T, Barrett JC, Hellmann MD. Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade. Cancer Discov. 2020 Dec;10(12):1842-1853. doi: 10.1158/2159-8290.CD-20-0047. Epub 2020 Aug 14.
- Derived from this study: PubMed 32339189Zajac M, Ye J, Mukhopadhyay P, Jin X, Ben Y, Antal J, Gupta AK, Rebelatto MC, Williams JA, Walker J. Optimal PD-L1-high cutoff for association with overall survival in patients with urothelial cancer treated with durvalumab monotherapy. PLoS One. 2020 Apr 27;15(4):e0231936. doi: 10.1371/journal.pone.0231936. eCollection 2020.
- Derived from this study: PubMed 31916448Nordstrom BL, Oguz M, Chu BC, Ouwens M, Arkenau HT, Klein AB. Effectiveness of durvalumab versus chemotherapy in metastatic urothelial cancer: an observational, indirect comparison. J Comp Eff Res. 2020 Feb;9(3):191-199. doi: 10.2217/cer-2019-0163. Epub 2020 Jan 9.
- Derived from this study: PubMed 31228626Antonia SJ, Balmanoukian A, Brahmer J, Ou SI, Hellmann MD, Kim SW, Ahn MJ, Kim DW, Gutierrez M, Liu SV, Schoffski P, Jager D, Jamal R, Jerusalem G, Lutzky J, Nemunaitis J, Calabro L, Weiss J, Gadgeel S, Bhosle J, Ascierto PA, Rebelatto MC, Narwal R, Liang M, Xiao F, Antal J, Abdullah S, Angra N, Gupta AK, Khleif SN, Segal NH. Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC. J Thorac Oncol. 2019 Oct;14(10):1794-1806. doi: 10.1016/j.jtho.2019.06.010. Epub 2019 Jun 20.
- Derived from this study: PubMed 31060602Althammer S, Tan TH, Spitzmuller A, Rognoni L, Wiestler T, Herz T, Widmaier M, Rebelatto MC, Kaplon H, Damotte D, Alifano M, Hammond SA, Dieu-Nosjean MC, Ranade K, Schmidt G, Higgs BW, Steele KE. Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy. J Immunother Cancer. 2019 May 6;7(1):121. doi: 10.1186/s40425-019-0589-x.
- Derived from this study: PubMed 30731276Segal NH, Ou SI, Balmanoukian A, Fury MG, Massarelli E, Brahmer JR, Weiss J, Schoffski P, Antonia SJ, Massard C, Zandberg DP, Khleif SN, Xiao F, Rebelatto MC, Steele KE, Robbins PB, Angra N, Song X, Abdullah S, Butler M. Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. Eur J Cancer. 2019 Mar;109:154-161. doi: 10.1016/j.ejca.2018.12.029. Epub 2019 Feb 4.
- Derived from this study: PubMed 30457897Zajac M, Boothman AM, Ben Y, Gupta A, Jin X, Mistry A, Sabalos C, Nielsen A, Manriquez G, Barker C, Antal J, Wang P, Patil P, Schechter N, Rebelatto MC, Walker J. Analytical Validation and Clinical Utility of an Immunohistochemical Programmed Death Ligand-1 Diagnostic Assay and Combined Tumor and Immune Cell Scoring Algorithm for Durvalumab in Urothelial Carcinoma. Arch Pathol Lab Med. 2019 Jun;143(6):722-731. doi: 10.5858/arpa.2017-0555-OA. Epub 2018 Nov 20.
- Derived from this study: PubMed 29510739Steele KE, Tan TH, Korn R, Dacosta K, Brown C, Kuziora M, Zimmermann J, Laffin B, Widmaier M, Rognoni L, Cardenes R, Schneider K, Boutrin A, Martin P, Zha J, Wiestler T. Measuring multiple parameters of CD8+ tumor-infiltrating lymphocytes in human cancers by image analysis. J Immunother Cancer. 2018 Mar 6;6(1):20. doi: 10.1186/s40425-018-0326-x.
- Derived from this study: PubMed 28817753Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411. doi: 10.1001/jamaoncol.2017.2411. Epub 2017 Sep 14.
- CSP amendmentLink provided by the sponsor.
- SAP redactedLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MedImmune, LLC
MedImmune LLC
79 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MEDI4736 in people with Advanced Solid Tumors, run by MedImmune LLC at 79 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 79 sites in United States, South Korea, Germany, Italy, United Kingdom and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase (time frame: For MEDI4736 0.1 to MEDI4736 10 mg/kg arms: from Day 1 to Day 28 of first dose; for MEDI4736 15 mg/kg arm: from Day 1 to Day 42 of first dose). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01693562, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2021; AzTrials last refreshed its copy on 31 Oct 2026.