Clinical trial
A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors
Name
D419NC00001
Description
This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, pharmacokinetic (PK), pharmacodynamics, and immunogenicity of durvalumab (MEDI4736) in combination with monalizumab (IPH2201) in adult participants with selected advanced solid tumors and the combination of durvalumab and monalizumab (IPH2201) standard of care systemic therapy with or without biological agent and monalizumab (IPH2201) with biological agent administered to participants with recurrent or metastatic colorectal cancer (CRC).
Trial arms
Trial start
2016-02-22
Estimated PCD
2021-10-26
Trial end
2024-09-02
Status
Active (not recruiting)
Phase
Early phase I
Treatment
Monalizumab
Participants will receive IV infusion of monalizumab as stated in arm description.
Arms:
Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W, Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W, Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W, Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W, Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W, Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS), Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC), Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC), Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (ovarian), Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W, Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W, Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W, Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W, Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W, Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W
Durvalumab
Participants will receive IV infusion of durvalumab as stated in arm description.
Arms:
Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W, Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W, Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W, Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W, Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W, Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS), Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC), Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC), Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (ovarian), Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W, Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W, Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W, Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W
Cetuximab
Participants will receive IV infusion of cetuximab as stated in arm description.
Arms:
Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W, Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W, Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W, Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W, Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W
mFOLFOX6
Participants will receive IV infusion of mFOLFOX as stated in arm description.
Arms:
Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W, Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W
Bevacizumab
Participants will receive IV infusion of bevacizumab as stated in arm description.
Arms:
Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W
Size
383
Primary endpoint
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Day 1 through 246.9 weeks (maximum observed duration)
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change From Baseline in Respiratory Rate (RR)
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change From Baseline in Pulse Rate (PR)
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change From Baseline in Body Temperature (BT)
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change From Baseline in Oxygen Saturation (OS)
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Number of Participants With Notable Change in QTcF and QTcB From Baseline
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters
Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Number of Participants With Dose Limiting Toxicities (DLTs)
From Day 1 to 28 days after the first dose of study drugs
Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B
Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
Eligibility criteria
Inclusion Criteria:
1. Participants must have histologic documentation of advanced recurrent or metastatic cancer.
2. Participants must be at the recurrent/metastatic setting, with selected advanced solid tumors.
3. Participants must have at least one lesion that is measurable by RECIST v1.1
4. Part 3, Dose exploration, CRC participants can be treatment naïve but should not have received more than two line of systemic therapy in the recurrent/metastatic setting.
Exclusion Criteria
1. Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may be permitted upon discussion with the medical monitor.
2. Prior participation in clinical studies that include durvalumab alone or in combination, where the study has registrational intent and the analyses for the primary endpoint have not yet been completed
3. Receipt of any conventional or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment
4. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 383, 'type': 'ACTUAL'}}
Updated at
2024-04-30
1 organization
5 products
1 indication
Organization
MedImmuneProduct
MonalizumabIndication
CancerProduct
CetuximabProduct
BevacizumabProduct
DurvalumabProduct
mFOLFOX6