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 Participants With Select Advanced Malignancies
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
Phase
Phase 1/Phase 2Lead Sponsor
MedImmuneStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Select Advanced Malignancies Kidney Cancer Clear Cell Renal Cell CarcinomaIntervention/Treatment
durvalumab nivolumab medi0680 ...Study Participants
97To evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Participants with Select Advanced Malignancies.
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.
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.
Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
Participants will receive IV infusion of nivolumab 240 mg Q2W in dose-expansion phase.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Inclusion Criteria: 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 Exclusion Criteria: 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
| Event Type | Organ System | Event Term | MEDI0680 0.1 mg/kg + Durvalumab 3 mg | MEDI0680 0.1 mg/kg + Durvalumab 10 mg | MEDI0680 0.5 mg/kg + Durvalumab 10 mg | MEDI0680 2.5 mg/kg + Durvalumab 10 mg | MEDI0680 10 mg/kg + Durvalumab 10 mg | MEDI0680 20 mg/kg + Durvalumab 10 mg | MEDI0680 20 mg/kg | MEDI0680 20 mg/kg + Durvalumab 750 mg | Nivolumab 240 mg |
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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 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 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 in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Number of participants in dose-expansion phase with abnormal ECG parameters reported as TEAEs are reported.
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.
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.
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).
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).
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.
