Solid TumorsPhase 1NCT02503774
MEDI9447 Alone and in Combination With MEDI4736 in Adult Participants With Select Advanced Solid Tumors.
A Phase 1 study testing Oleclumab and Durvalumab in people with Solid Tumors, run by MedImmune LLC at 18 sites in 3 countries.
Trial summary
The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination with MEDI4736 in Adult Participants with Select Advanced Solid Tumors Read more about this study
- Who is it for?
- Ages 18 to 101 years
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Oleclumab and Durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 18 sitesin 3 countries
- Study dates
- 24 Jul 2015to 7 Mar 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 101 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult participants; age ≥ 18
- Written and signed informed consent must be obtained
- Have histologic or cytologic documentation of solid tumor including EGFRm NSCLC
- Participants must have at least 1 lesion that is measurable using RECIST guidelines
- Participants must consent to provide archived tumor specimens or tumor biopsies for correlative biomarker studies.
- Eastern Cooperative Oncology Group performance score of 0 or 1
- Adequate organ function
Who cannot join
- Prior treatment with tumor necrosis factor receptor superfamily agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR). One cohort also excludes anti CTLA-4, PD-L1, and anti PD-L1.
- Participants who have received prior therapy with regimens containing CTLA-4, PD-L1, or PD-1 antagonists may be permitted to enroll under certain conditions
- Cardiac or peripheral vascular disease meeting any of the following criteria:
- Past history of myocardial infarction in the prior 12 months
- Past history of stroke or transient ischemic attack requiring medical therapy
- Congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification
Show all 14Show fewer
- Grade 3 or greater edema (eg, peripheral, pulmonary)
- History of Grade 3 or greater thromboembolic events in the prior 12 months
- Participants with active tuberculosis are ineligible. In settings where there is clinical or radiographic evidence of tuberculosis, active disease must be ruled out
- Active or prior documented autoimmune or inflammatory disorders
- Untreated central nervous system (CNS) metastatic disease
- Known positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or active hepatitis A or C
- Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, ductal carcinoma in situ of the breast that has been surgically cured
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, uncontrolled hypertension, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with study requirement
Trial locations and contacts
18 sites in 3 countries.
18 sites in 3 countries
United States11 sites
Research Site
Atlanta, Georgia, 30318
Research Site
Cincinnati, Ohio, 45267
Research Site
Columbus, Ohio, 43210
Research Site
Dallas, Texas, 75230
Research Site
Durham, North Carolina, 27705
Research Site
Gainesville, Florida, 32610
Research Site
Houston, Texas, 77030
Research Site
La Jolla, California, 92093
Research Site
Nashville, Tennessee, 37203
Research Site
New Haven, Connecticut, 06510
Research Site
St Louis, Missouri, 63156
Australia4 sites
Research Site
Camperdown, 2050
Research Site
Parkville, 3050
Research Site
St Leonards, 2065
Research Site
Woolloongabba, 4068
South Korea3 sites
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Seoul, 06351
About this study
Official title: A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors
The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination with MEDI4736 in Adult Participants with Select Advanced Solid Tumors
- Conditions
- Solid Tumors
- Being tested
- Oleclumab, Durvalumab
- Keywords
- Solid Tumors,, MEDI9447,, oleclumab,, MEDI4736,, durvalumab,, CD73,, programmed death ligand-1 (PD-L1),, epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC),, immunotherapy,, pancreatic,, colorectal
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OleclumabDrug
Participants will receive IV infusion of oleclumab as stated in arms' description.
DurvalumabDrug
Participants will receive IV infusion of durvalumab as stated in arms' description.
| Study group | Role | What they receive |
|---|---|---|
| Dose-escalation: Oleclumab Dose 1 | Experimental | Participants will receive oleclumab Dose 1 intravenously (IV) every two weeks (Q2W) until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab |
| Dose-escalation: Oleclumab Dose 2 | Experimental | Participants will receive oleclumab Dose 2 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab |
| Dose-escalation: Oleclumab Dose 3 | Experimental | Participants will receive oleclumab Dose 3 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab |
| Dose-escalation: Oleclumab Dose 4 | Experimental | Participants will receive oleclumab Dose 4 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab |
| Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1 | Experimental | Participants will receive oleclumab Dose 1 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab; Drug: Durvalumab |
| Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1 | Experimental | Participants will receive oleclumab Dose 2 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab; Drug: Durvalumab |
| Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1 | Experimental | Participants will receive oleclumab Dose 3 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab; Drug: Durvalumab |
| Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1 | Experimental | Participants will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab; Drug: Durvalumab |
| Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1 | Experimental | Participants with previously treated microsatellite stable-colorectal cancer (MSS-CRC) will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab; Drug: Durvalumab |
| Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1 | Experimental | Participants with previously treated pancreatic adenocarcinoma will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab; Drug: Durvalumab |
| Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1 | Experimental | Participants with previously treated EGFRm NSCLC will receive oleclumab Dose 4 IV followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Drug: Oleclumab; Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs) in Dose-escalation Phase
A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period, which included any Grade 4 immune-mediated adverse event (imAE), any >= Grade 3 colitis, any Grade 3 or 4 non-infectious pneumonitis irrespective of duration, any Grade 3 imAE (excluding colitis or pneumonitis, did not downgrade to <= Grade 2 within 3 days after onset of the event despite maximal medical supportive care including systemic corticosteroids or did not downgrade to <= Grade 1 or baseline within 14 days), liver transaminase elevation >= 5 × but <= 8 × upper limit of normal (ULN) that did not downgrade to Grade 2 within 5 days after onset with optimal medical management (including systemic corticosteroids), transaminase elevation > 8 × ULN or total bilirubin (TBL) > 5 × ULN regardless of duration or reversibility, or any increase in aspartate aminotransferase or alanine aminotransferase > 3 × ULN and concurrent increase in TBL > 2 × ULN (Hy's Law).
Measured: From Day 1 to Day 28 after first dose of study drug
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An 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 200.1 weeks (corresponding to maximum observed duration)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, coagulation, and urinalysis.
Measured: From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported.
Measured: From Day 1 through 188.1 weeks (corresponding to maximum observed duration)
Number of Participants With Change From Baseline in QTcF
Number of participants with change from Baseline in QTcF (> 60 msec and > 90 msec) is reported.
Measured: Baseline (prior to Day 1 dose) through 188.1 weeks (corresponding to maximum observed duration)
Secondary outcomes (17)
Percentage of Participants With Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
The OR is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. 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 the diameters of target lesions compared to baseline, and the non-target lesion at least stable with no evidence of new lesions. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. Percentage of participants with OR are reported.
Measured: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Percentage pf Participants With Disease Control (DC) per RECIST v1.1
The DC is defined as CR, PR, or stable disease (SD) which was maintained by >= 8 weeks from the start of treatment. The SD is defined as neither sufficient shrinkage of target lesion to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study and non-progressive disease and not evaluable or no non-target lesion. 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 the diameters of target lesions compared to baseline, and the non-target lesion at least stable with no evidence of new lesions. Percentage of participants with DC at >= 8 weeks, >= 16 weeks, and >= 24 weeks are reported.
Measured: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Duration of Response (DoR) per RECIST v1.1
The DoR is defined as the duration from the first documentation of OR (confirmed CR or PR) to the first documented PD or death due to any cause, whichever occurred first. 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 the diameters of target lesions compared to baseline, and the non-target lesion at least stable with no evidence of new lesions. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. The PD is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The DoR was estimated using Kaplan-Meier method.
Measured: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Progression-Free Survival (PFS)
The PFS is defined as the time from the start of study treatment until the documentation of PD based on RECIST version 1.1 or death due to any cause, whichever occurred first. The PD is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The PFS was estimated using Kaplan-Meier method.
Measured: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Overall Survival (OS)
The OS is defined as the time from the start of treatment with study drug until death due to any cause. The OS was estimated using Kaplan-Meier method.
Measured: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Maximum Observed Serum Concentration (Cmax) of MEDI9447
The Cmax of MEDI9447 (oleclumab) for Cycle 1 and at steady state (Day 57) are reported.
Measured: Day 1 (pre-dose, and 10 minutes and 2 hours post end of infusion), Day 57 (pre-dose and 10 minutes post end of infusion)
Area Under the Serum Concentration Time Curve From 0 To 14 Days Post First Dose [AUC(0-14)] of MEDI9447
The AUC(0-14) of MEDI9447 is reported.
Measured: Day 1 (pre-dose; 10 minutes and 2 hours post end of infusion)
Time To Maximum Observed Serum Concentration (Tmax) of MEDI9447
The Tmax of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 are reported.
Measured: Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
Observed Lowest Serum Concentration Reached Before the Next Dose (Ctrough) of MEDI9447
The Ctrough of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 are reported.
Measured: Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
Accumulation Ratio for Cmax (Rac Cmax) of MEDI9447
The Rac Cmax of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 is reported.
Measured: Day 57 (pre-dose; 10 minutes post end of infusion)
Accumulation Ratio for Ctrough (Rac Ctrough) of MEDI9447
The Rac Ctrough of MEDI9447 is reported.
Measured: Day 57 (pre-dose; 10 minutes post end of infusion)
Cmax of MEDI4736
The Cmax of MEDI4736 (durvalumab) is reported.
Measured: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
Tmax of MEDI4736
The Tmax of MEDI4736 is reported.
Measured: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
Ctrough of MEDI4736
The Ctrough of MEDI4736 for Cycle 1 and at steady state (Day 57) are reported.
Measured: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion), Day 57 (prior to start of MEDI9447 infusion)
Rac Ctrough of MEDI4736
The Rac Ctrough of MEDI4736 is reported.
Measured: Day 57 (prior to start of MEDI4736 infusion)
Number of Participants With Positive Anti-Drug Antibody Response (ADA) to MEDI9447
Number of participants with positive ADA to MEDI9447 is reported. Persistent positive was defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive was defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with < 16 weeks between first and last positive).
Measured: Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
Number of Participants With Positive ADA to MEDI4736
Number of participants with positive ADA to MEDI4736 is reported. Persistent positive was defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive was defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with < 16 weeks between first and last positive).
Measured: Day 1 through 200.1 weeks (Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study start24 Jul 2015
- Primary completion22 Jan 2021
- Study completion7 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MedImmune LLC, Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02503774
- Sponsor's protocol ID
- D6070C00001
- Status last verified
- Jul 2023
- First submitted
- 6 Jul 2015
- Last updated
- 11 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Bendell J, LoRusso P, Overman M, Noonan AM, Kim DW, Strickler JH, Kim SW, Clarke S, George TJ, Grimison PS, Barve M, Amin M, Desai J, Wise-Draper T, Eck S, Jiang Y, Khan AA, Wu Y, Martin P, Cooper ZA, Elgeioushi N, Mueller N, Kumar R, Patel SP. First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. Cancer Immunol Immunother. 2023 Jul;72(7):2443-2458. doi: 10.1007/s00262-023-03430-6. Epub 2023 Apr 5.
PubMed 37016126Hay CM, Sult E, Huang Q, Mulgrew K, Fuhrmann SR, McGlinchey KA, Hammond SA, Rothstein R, Rios-Doria J, Poon E, Holoweckyj N, Durham NM, Leow CC, Diedrich G, Damschroder M, Herbst R, Hollingsworth RE, Sachsenmeier KF. Targeting CD73 in the tumor microenvironment with MEDI9447. Oncoimmunology. 2016 Jul 11;5(8):e1208875. doi: 10.1080/2162402X.2016.1208875. eCollection 2016 Aug.
PubMed 27622077
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02503774
- Acronym / sponsor ID
- D6070C00001
- Conditions
- Solid Tumors
- Keywords
- Solid Tumors,, MEDI9447,, oleclumab,, MEDI4736,, durvalumab,, CD73,, programmed death ligand-1 (PD-L1),, epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC),
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 24 Jul 2015 (actual)
- Primary completion
- 22 Jan 2021 (actual)
- Study completion
- 7 Mar 2023 (actual)
- First posted
- 21 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination with MEDI4736 in Adult Participants with Select Advanced Solid Tumors
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation: Oleclumab Dose 1 | Experimental | Drug: OleclumabParticipants will receive oleclumab Dose 1 intravenously (IV) every two weeks (Q2W) until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 2 | Experimental | Drug: OleclumabParticipants will receive oleclumab Dose 2 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 3 | Experimental | Drug: OleclumabParticipants will receive oleclumab Dose 3 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 4 | Experimental | Drug: OleclumabParticipants will receive oleclumab Dose 4 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1 | Experimental | Drug: Oleclumab, Drug: DurvalumabParticipants will receive oleclumab Dose 1 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1 | Experimental | Drug: Oleclumab, Drug: DurvalumabParticipants will receive oleclumab Dose 2 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1 | Experimental | Drug: Oleclumab, Drug: DurvalumabParticipants will receive oleclumab Dose 3 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1 | Experimental | Drug: Oleclumab, Drug: DurvalumabParticipants will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1 | Experimental | Drug: Oleclumab, Drug: DurvalumabParticipants with previously treated microsatellite stable-colorectal cancer (MSS-CRC) will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1 | Experimental | Drug: Oleclumab, Drug: DurvalumabParticipants with previously treated pancreatic adenocarcinoma will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
| Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1 | Experimental | Drug: Oleclumab, Drug: DurvalumabParticipants with previously treated EGFRm NSCLC will receive oleclumab Dose 4 IV followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first. |
Who may qualify
- Ages
- 18 to 101 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult participants; age ≥ 18
- Written and signed informed consent must be obtained
- Have histologic or cytologic documentation of solid tumor including EGFRm NSCLC
- Participants must have at least 1 lesion that is measurable using RECIST guidelines
- Participants must consent to provide archived tumor specimens or tumor biopsies for correlative biomarker studies.
Key exclusion criteria (14 listed)
- Prior treatment with tumor necrosis factor receptor superfamily agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR). One cohort also excludes anti CTLA-4, PD-L1, and anti PD-L1.
- Participants who have received prior therapy with regimens containing CTLA-4, PD-L1, or PD-1 antagonists may be permitted to enroll under certain conditions
- Cardiac or peripheral vascular disease meeting any of the following criteria:
- Grade 3 or greater edema (eg, peripheral, pulmonary)
- History of Grade 3 or greater thromboembolic events in the prior 12 months
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 |
|---|---|---|
| OleclumabParticipants will receive IV infusion of oleclumab as stated in arms' description. | Drug | Dose-escalation: Oleclumab Dose 1, Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1, Dose-escalation: Oleclumab Dose 2, Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1, Dose-escalation: Oleclumab Dose 3, Dose-escalation: Oleclumab Dose 4, Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1, Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1, Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1, Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1, Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1 |
| DurvalumabParticipants will receive IV infusion of durvalumab as stated in arms' description. | Drug | Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1, Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1, Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1, Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1, Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1, Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1, Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1 |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs) in Dose-escalation Phase
Time frame: From Day 1 to Day 28 after first dose of study drug
A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period, which included any Grade 4 immune-mediated adverse event (imAE), any >= Grade 3 colitis, any Grade 3 or 4 non-infectious pneumonitis irrespective of duration, any Grade 3 imAE (excluding colitis or pneumonitis, did not downgrade to <= Grade 2 within 3 days after onset of the event despite maximal medical supportive care including systemic corticosteroids or did not downgrade to <= Grade 1 or baseline within 14 days), liver transaminase elevation >= 5 × but <= 8 × upper limit of normal (ULN) that did not downgrade to Grade 2 within 5 days after onset with optimal medical management (including systemic corticosteroids), transaminase elevation > 8 × ULN or total bilirubin (TBL) > 5 × ULN regardless of duration or reversibility, or any increase in aspartate aminotransferase or alanine aminotransferase > 3 × ULN and concurrent increase in TBL > 2 × ULN (Hy's Law).
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
An 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
Time frame: From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, coagulation, and urinalysis.
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Time frame: From Day 1 through 188.1 weeks (corresponding to maximum observed duration)
Participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported.
Number of Participants With Change From Baseline in QTcF
Time frame: Baseline (prior to Day 1 dose) through 188.1 weeks (corresponding to maximum observed duration)
Number of participants with change from Baseline in QTcF (> 60 msec and > 90 msec) is reported.
17 secondary outcomes
Percentage of Participants With Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Percentage pf Participants With Disease Control (DC) per RECIST v1.1
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Duration of Response (DoR) per RECIST v1.1
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Progression-Free Survival (PFS)
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Overall Survival (OS)
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Maximum Observed Serum Concentration (Cmax) of MEDI9447
Time frame: Day 1 (pre-dose, and 10 minutes and 2 hours post end of infusion), Day 57 (pre-dose and 10 minutes post end of infusion)
Area Under the Serum Concentration Time Curve From 0 To 14 Days Post First Dose [AUC(0-14)] of MEDI9447
Time frame: Day 1 (pre-dose; 10 minutes and 2 hours post end of infusion)
Time To Maximum Observed Serum Concentration (Tmax) of MEDI9447
Time frame: Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
Observed Lowest Serum Concentration Reached Before the Next Dose (Ctrough) of MEDI9447
Time frame: Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
Accumulation Ratio for Cmax (Rac Cmax) of MEDI9447
Time frame: Day 57 (pre-dose; 10 minutes post end of infusion)
Accumulation Ratio for Ctrough (Rac Ctrough) of MEDI9447
Time frame: Day 57 (pre-dose; 10 minutes post end of infusion)
Cmax of MEDI4736
Time frame: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
Tmax of MEDI4736
Time frame: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
Ctrough of MEDI4736
Time frame: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion), Day 57 (prior to start of MEDI9447 infusion)
Rac Ctrough of MEDI4736
Time frame: Day 57 (prior to start of MEDI4736 infusion)
Number of Participants With Positive Anti-Drug Antibody Response (ADA) to MEDI9447
Time frame: Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
Number of Participants With Positive ADA to MEDI4736
Time frame: Day 1 through 200.1 weeks (Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2023.
- Derived from this study: PubMed 37016126Bendell J, LoRusso P, Overman M, Noonan AM, Kim DW, Strickler JH, Kim SW, Clarke S, George TJ, Grimison PS, Barve M, Amin M, Desai J, Wise-Draper T, Eck S, Jiang Y, Khan AA, Wu Y, Martin P, Cooper ZA, Elgeioushi N, Mueller N, Kumar R, Patel SP. First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. Cancer Immunol Immunother. 2023 Jul;72(7):2443-2458. doi: 10.1007/s00262-023-03430-6. Epub 2023 Apr 5.
- Derived from this study: PubMed 27622077Hay CM, Sult E, Huang Q, Mulgrew K, Fuhrmann SR, McGlinchey KA, Hammond SA, Rothstein R, Rios-Doria J, Poon E, Holoweckyj N, Durham NM, Leow CC, Diedrich G, Damschroder M, Herbst R, Hollingsworth RE, Sachsenmeier KF. Targeting CD73 in the tumor microenvironment with MEDI9447. Oncoimmunology. 2016 Jul 11;5(8):e1208875. doi: 10.1080/2162402X.2016.1208875. eCollection 2016 Aug.
- study-synopsis\_RedactedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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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 study director
MedImmune LLC
18 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Oleclumab and Durvalumab in people with Solid Tumors, run by MedImmune LLC at 18 sites in 3 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 7 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 11 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Australia, South Korea. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 (DLTs) in Dose-escalation Phase (time frame: From Day 1 to Day 28 after first dose of study drug). The study lists 5 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 NCT02503774, which also lists 2 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 11 Jul 2023.