Select Advanced MalignanciesPhase 1/2NCT02118337
A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination With Durvalumab Versus Nivolumab Monotherapy in Participants With Select Advanced Malignancies
A Phase 1/2 study testing MEDI0680, Durvalumab and Nivolumab in people with Select Advanced Malignancies and Kidney Cancer, run by MedImmune LLC at 27 sites in 6 countries.
Trial summary
To evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Participants with Select Advanced Malignancies. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Select Advanced Malignancies, Kidney Cancer, Clear Cell Renal Cell Carcinoma
- What is being tested?
- MEDI0680, Durvalumab and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 27 sitesin 6 countries
- Study dates
- 19 May 2014to 17 Mar 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
- Must be 18 years or older
- Eastern Cooperative Oncology Group performance status of 0-1
- Adequate organ function
- At least 1 prior line of therapy
Who cannot join
- Concurrent enrollment in another clinical study, unless in follow-up period or it is an observational study
- Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
- Prior treatment with immunotherapy
Trial locations and contacts
27 sites in 6 countries.
27 sites in 6 countries
United States13 sites
Research Site
Cleveland, Ohio, 44195
Research Site
Hackensack, New Jersey, 07601
Research Site
Hershey, Pennsylvania, 17033-0850
Research Site
Los Angeles, California, 90025
Research Site
Louisville, Kentucky, 40202
Research Site
Nashville, Tennessee, 37203
Research Site
New York, New York, 10065
Research Site
Oklahoma City, Oklahoma, 73104
Research Site
Overland Park, Kansas, 66209
Research Site
Portland, Oregon, 97213
Research Site
Rochester, Minnesota, 55905
Research Site
Seattle, Washington, 98109
Research Site
Tampa, Florida, 33612
France5 sites
Research Site
Bordeaux, 33075
Research Site
Dijon, 21079
Research Site
Marseille, 13009
Research Site
Paris, 75908
Research Site
Villejuif, 94805
United Kingdom3 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Cardiff, CF14 2TL
Research Site
Southampton, SO16 6YD
Australia2 sites
Research Site
East Bentleigh, 3165
Research Site
Frankston, 3199
Canada2 sites
Research Site
Montreal, Quebec, H3T 1E2
Research Site
Toronto, Ontario, M5G 2M9
Netherlands2 sites
Research Site
Amsterdam, 1066 CX
Research Site
Groningen, 9713 GZ
About this study
Official title: A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination With Durvalumab Versus Nivolumab Monotherapy in Subjects With Select Advanced Malignancies
To evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Participants with Select Advanced Malignancies.
Read the detailed description
This is a multicenter, open-label, Phase 1/2 study to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of MEDI0680 in combination with durvalumab or nivolumab monotherapy in adult immunotherapy-naïve participants with selected advanced malignancies.
- Being tested
- MEDI0680, Durvalumab, Nivolumab
- Keywords
- select advanced malignancies,, kidney cancer,, clear cell renal cell carcinoma
- Medical subject headings
- Kidney Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI0680Biological
Also called AMP-514
Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
DurvalumabBiological
Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
NivolumabBiological
Participants will receive IV infusion of nivolumab 240 mg Q2W in dose-expansion phase.
| Study group | Role | What they receive |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg/kg | Experimental | Participants in dose-escalation phase will receive IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. Receives: Biological: MEDI0680; Biological: Durvalumab |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Experimental | Participants in dose-escalation phase will receive IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Receives: Biological: MEDI0680; Biological: Durvalumab |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Experimental | Participants in dose-escalation phase will receive IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Receives: Biological: MEDI0680; Biological: Durvalumab |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Experimental | Participants in dose-escalation phase will receive IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Receives: Biological: MEDI0680; Biological: Durvalumab |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Experimental | Participants in dose-escalation phase will receive IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Receives: Biological: MEDI0680; Biological: Durvalumab |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Experimental | Participants in dose-escalation phase will receive IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. Receives: Biological: MEDI0680; Biological: Durvalumab |
| MEDI0680 20 mg/kg | Experimental | Participants in dose-expansion phase will receive IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Receives: Biological: MEDI0680 |
| MEDI0680 20 mg/kg + Durvalumab 750 mg | Experimental | Participants in dose-expansion phase will receive IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Receives: Biological: MEDI0680; Biological: Durvalumab |
| Nivolumab 240 mg | Active comparator | Participants in dose-expansion phase will receive IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. Receives: Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase
Number of participants in dose-escalation phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters are defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine.
Measured: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase
Number of participants in dose-escalation phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight.
Measured: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase
Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported.
Measured: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose-expansion Phase
The ORR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. 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 non-target lesion. 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.
Measured: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Secondary outcomes (24)
Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE) based on RECIST v1.1. 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% decrease 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 baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
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 4 weeks 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) that were separated by at least 4 weeks 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. The DCR at >= 8 weeks and >=24 weeks are reported.
Measured: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method.
Measured: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method.
Measured: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
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 PFS was estimated using Kaplan-Meier method.
Measured: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Overall Survival in Dose-expansion Phase
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 baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
The BOR includes CR, PR, SD, PD, and NE per Modified RECIST v1.1. 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% decrease 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 baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
The ORR is defined as best overall response of confirmed CR or confirmed PR based on modified RECIST v1.1. 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 non-target lesion. 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.
Measured: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on modified 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 4 weeks 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) that were separated by at least 4 weeks 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. The DCR at >= 8 weeks and >=24 weeks are reported.
Measured: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) based on modified 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method.
Measured: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
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 modified 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 4 weeks 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) that were separated by at least 4 weeks with no evidence of progression in-between. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method.
Measured: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on modified RECIST v1.1 or death due to any cause, whichever occurred first. The PFS was estimated using Kaplan-Meier method.
Measured: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
OS in Dose-escalation Phase
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 baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
Number of Participants With TEAEs and TESAEs in Dose-expansion Phase
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase
Number of participants in dose-expansion phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine.
Measured: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase
Number of participants in dose-expansion phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight.
Measured: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase
Number of participants in dose-expansion phase with abnormal ECG parameters reported as TEAEs are reported.
Measured: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Antitumor Activity of MEDI0680 and Durvalumab Versus Nivolumab Monotherapy in Immunotherapy-Naïve Participants With Advanced or Metastatic Clear-cell Renal Cell Carcinoma (ccRCC) Based on Blinded Independent Central Review (BICR) in Dose-expansion Phase
Measured: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Percent Change From Baseline in Tumor Size in Dose-escalation Phase (Based on Investigator-assessed Modified RECIST v1.1) and Dose-expansion Phase (Based on Investigator-assessed RECIST v1.1)
Measured: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant for dose-escalation phase and approximately 5 years 10 months for dose-expansion phase)
Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases
Serum concentration of MEDI0680 were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration.
Measured: Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases
Serum concentration of durvalumab were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration.
Measured: Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases
Number of participants with positive ADAs to MEDI0680 are reported. 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. Transient positive is 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: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)
Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases
Number of participants with positive ADA to durvalumab are reported. 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. Transient positive is 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: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)
ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase
ORR for participants with PD-L1 status positive and negative are reported. The ORR is defined as best overall response 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. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. 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.
Measured: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study start19 May 2014
- Primary completion17 Mar 2020
- Study completion17 Mar 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 (1)Papers the sponsor has linked to this study.
- Other trials for Select Advanced MalignanciesStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Laura Chow, MD, Principal investigator, University of WashingtonOmid Hamid, MD, Principal investigator, The Angeles ClinicJhanelle Gray, MD, Principal investigator, Moffitt Cancer CenterRachel Sanborn, MD, Principal investigator, Providence Cancer CenterMohamad Salkeni, MD, Principal investigator, Mary Babb Randolph Cancer CenterMonika Joshi, MD, Principal investigator, Penn State Hershey Cancer InstituteRobert Alter, MD, Principal investigator, John Theurer Cancer CenterRaid Aljumaily, MD, Principal investigator, Peggy Charles Stephenson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02118337
- Sponsor's protocol ID
- D6020C00001
- Status last verified
- May 2021
- First submitted
- 11 Apr 2014
- Last updated
- 1 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- 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
Voss MH, Azad AA, Hansen AR, Gray JE, Welsh SJ, Song X, Kuziora M, Meinecke L, Blando J, Achour I, Wang Y, Walcott FL, Oosting SF. A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Clin Cancer Res. 2022 Jul 15;28(14):3032-3041. doi: 10.1158/1078-0432.CCR-21-4115.
PubMed 35507017
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination With Durvalumab Versus Nivolumab Monotherapy in Subjects With Select Advanced Malignancies
- ClinicalTrials.gov ID
- NCT02118337
- Acronym / sponsor ID
- D6020C00001
- Keywords
- select advanced malignancies,, kidney cancer,, clear cell renal cell carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 19 May 2014 (actual)
- Primary completion
- 17 Mar 2020 (actual)
- Study completion
- 17 Mar 2020 (actual)
- First posted
- 21 Apr 2014 (estimated)
- Results
- Posted 1 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Participants with Select Advanced Malignancies.
Detailed description
This is a multicenter, open-label, Phase 1/2 study to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of MEDI0680 in combination with durvalumab or nivolumab monotherapy in adult immunotherapy-naïve participants with selected advanced malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg/kg | Experimental | Biological: MEDI0680, Biological: DurvalumabParticipants in dose-escalation phase will receive IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months. |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Experimental | Biological: MEDI0680, Biological: DurvalumabParticipants in dose-escalation phase will receive IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Experimental | Biological: MEDI0680, Biological: DurvalumabParticipants in dose-escalation phase will receive IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Experimental | Biological: MEDI0680, Biological: DurvalumabParticipants in dose-escalation phase will receive IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Experimental | Biological: MEDI0680, Biological: DurvalumabParticipants in dose-escalation phase will receive IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Experimental | Biological: MEDI0680, Biological: DurvalumabParticipants in dose-escalation phase will receive IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. |
| MEDI0680 20 mg/kg | Experimental | Biological: MEDI0680Participants in dose-expansion phase will receive IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. |
| MEDI0680 20 mg/kg + Durvalumab 750 mg | Experimental | Biological: MEDI0680, Biological: DurvalumabParticipants in dose-expansion phase will receive IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. |
| Nivolumab 240 mg | Active comparator | Biological: NivolumabParticipants in dose-expansion phase will receive IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Must be 18 years or older
- Eastern Cooperative Oncology Group performance status of 0-1
- Adequate organ function
- At least 1 prior line of therapy
Key exclusion criteria (3 listed)
- Concurrent enrollment in another clinical study, unless in follow-up period or it is an observational study
- Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
- Prior treatment with immunotherapy
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 |
|---|---|---|
| MEDI0680Also: AMP-514Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase. | Biological | MEDI0680 0.1 mg/kg + Durvalumab 10 mg, MEDI0680 0.1 mg/kg + Durvalumab 3 mg/kg, MEDI0680 0.5 mg/kg + Durvalumab 10 mg, MEDI0680 10 mg/kg + Durvalumab 10 mg, MEDI0680 2.5 mg/kg + Durvalumab 10 mg, MEDI0680 20 mg/kg, MEDI0680 20 mg/kg + Durvalumab 10 mg, MEDI0680 20 mg/kg + Durvalumab 750 mg |
| DurvalumabParticipants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase. | Biological | MEDI0680 0.1 mg/kg + Durvalumab 10 mg, MEDI0680 0.1 mg/kg + Durvalumab 3 mg/kg, MEDI0680 0.5 mg/kg + Durvalumab 10 mg, MEDI0680 10 mg/kg + Durvalumab 10 mg, MEDI0680 2.5 mg/kg + Durvalumab 10 mg, MEDI0680 20 mg/kg + Durvalumab 10 mg, MEDI0680 20 mg/kg + Durvalumab 750 mg |
| NivolumabParticipants will receive IV infusion of nivolumab 240 mg Q2W in dose-expansion phase. | Biological | Nivolumab 240 mg |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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 Dose-escalation Phase
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of participants in dose-escalation phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters are defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine.
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of participants in dose-escalation phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight.
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported.
Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose-expansion Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
The ORR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. 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 non-target lesion. 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.
24 secondary outcomes
Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Overall Survival in Dose-expansion Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
OS in Dose-escalation Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
Number of Participants With TEAEs and TESAEs in Dose-expansion Phase
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Antitumor Activity of MEDI0680 and Durvalumab Versus Nivolumab Monotherapy in Immunotherapy-Naïve Participants With Advanced or Metastatic Clear-cell Renal Cell Carcinoma (ccRCC) Based on Blinded Independent Central Review (BICR) in Dose-expansion Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Percent Change From Baseline in Tumor Size in Dose-escalation Phase (Based on Investigator-assessed Modified RECIST v1.1) and Dose-expansion Phase (Based on Investigator-assessed RECIST v1.1)
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant for dose-escalation phase and approximately 5 years 10 months for dose-expansion phase)
Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases
Time frame: Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases
Time frame: Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)
Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)
ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35507017Voss MH, Azad AA, Hansen AR, Gray JE, Welsh SJ, Song X, Kuziora M, Meinecke L, Blando J, Achour I, Wang Y, Walcott FL, Oosting SF. A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Clin Cancer Res. 2022 Jul 15;28(14):3032-3041. doi: 10.1158/1078-0432.CCR-21-4115.
- Redacted Protocol D6020C00001Link provided by the sponsor.
- Redacted SAP D6020C00001Link 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.
Related trials for Select Advanced Malignancies
RecruitingPhase 2
Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select Subtypes of Advanced/Metastatic Soft-tissue Sarcoma
Phase 2, Zanzalintinib
RecruitingPhase 1
M0324 as Monotherapy and in Combination With Pembrolizumab or Chemotherapy in Participants With Selected Advanced Solid Tumors
Advanced Solid Tumor
RecruitingPhase 3
Study to Evaluate Efficacy and Safety of Firmonertinib Compared With Investigator's Choice of EGFR Inhibitor as First-Line Treatment in Participants Who Have Locally Advanced or Metastatic NSCLC With EGFR P-Loop and Alpha C-Helix Compressing (PACC) Uncommon Mutations
Non-Small-Cell Lung Cancer, Metastatic Non-Small-Cell Lung Cancer
RecruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8
RecruitingPhase 3
A Study Comparing BL-M05D1 With the Investigator's Choice of Treatment Regimen in Patients With Claudin (CLDN)18.2-Positive Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma (GC/GEJC) Who Have Received Prior First-Line Treatment
Gastric Cancer, Gastroesophageal Junction Adenocarcinoma
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.
Laura Chow, MD principal investigator
University of Washington
Omid Hamid, MD principal investigator
The Angeles Clinic
Jhanelle Gray, MD principal investigator
Moffitt Cancer Center
27 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MEDI0680, Durvalumab and Nivolumab in people with Select Advanced Malignancies and Kidney Cancer, run by MedImmune LLC at 27 sites in 6 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 4 inclusion and 3 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 1 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, France, United Kingdom, Australia, Canada and 1 more country. 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 1 Jun 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 Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase (time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)). 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 NCT02118337, which also lists 1 linked publication.
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 1 Jun 2021.