A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors
Study identifier:D419NC00001
ClinicalTrials.gov identifier:NCT02671435
EudraCT identifier:2016-000662-38
CTIS identifier:N/A
Recruitment Complete
Official Title
A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects with Select Advanced Solid Tumors
Medical condition
Advanced Solid Tumors
Phase
Phase 1/2
Healthy volunteers
No
Study drug
Monalizumab, Durvalumab, Cetuximab, mFOLFOX6, Bevacizumab
Sex
All
Actual Enrollment
383
Study type
Interventional
Age
18 Years - 99 Years
Date
Study Start Date: 22 Feb 2016
Primary Completion Date: 26 Oct 2021
Estimated Study Completion Date: 02 Sept 2024
Study design
Allocation: Randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Verification:
Verified 01 Jan 2024 by MedImmune, LLC
Sponsors
MedImmune, LLC
Collaborators
-
Inclusion and exclusion criteria
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No locations available
| Arms | Assigned Interventions |
|---|---|
| Experimental: Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W Participants will receive intravenous (IV) infusions of durvalumab 1500 mg every 4 weeks (Q4W) in combination with monalizumab 22.5 mg every 2 weeks (Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed disease progression (PD), or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. |
| Experimental: Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 75 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. |
| Experimental: Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 225 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. |
| Experimental: Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. |
| Experimental: Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W Participants will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q4W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. |
| Experimental: Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC) Participants with microsatellite-stable colorectal cancer (MSS-CRC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. |
| Experimental: Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (ovarian) Participants with ovarian cancer will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. |
| Experimental: Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) Participants with endometrial MSS will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. |
| Experimental: Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) Participants with non-small cell lung cancer (NSCLC) will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. |
| Experimental: Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W Participants with first-line (1L) MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus mFOLFOX (oxaliplatin 85 mg/m^2 IV infusion, folinic acid 400 mg/m^2 infusion, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of bevacizumab 5 mg/kg Q2W up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. Drug: mFOLFOX6 Participants will receive IV infusion of mFOLFOX as stated in arm description. Drug: Bevacizumab Participants will receive IV infusion of bevacizumab as stated in arm description. |
| Experimental: Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W Participants with 1L MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W, plus mFOLFOX6 (oxaliplatin 85 mg/m^2, folinic acid 400 mg/m^2, fluorouracil 400 mg/m^2 IV bolus, followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours on Day 1) Q2W plus IV infusion of cetuximab (loading dose of 400 mg/m^2 on Day 1, followed by maintenance dose of 250 mg/m^2 IV infusion every week starting on Day 8, then changed to 500 mg/m^2 IV infusion Q2W) up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. Drug: Cetuximab Participants will receive IV infusion of cetuximab as stated in arm description. Drug: mFOLFOX6 Participants will receive IV infusion of mFOLFOX as stated in arm description. |
| Experimental: Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W Participants with recurrent or metastatic third-line (3L) RAS mutant MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. Drug: Cetuximab Participants will receive IV infusion of cetuximab as stated in arm description. |
| Experimental: Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W Participants with recurrent or metastatic 3L RAS mutant MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Cetuximab Participants will receive IV infusion of cetuximab as stated in arm description. |
| Experimental: Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusions of durvalumab 1500 mg Q4W in combination with monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Durvalumab Participants will receive IV infusion of durvalumab as stated in arm description. Drug: Cetuximab Participants will receive IV infusion of cetuximab as stated in arm description. |
| Experimental: Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W Participants with recurrent or metastatic 3L RAS/BRAF wild type MSS-CRC will receive IV infusion of monalizumab 750 mg Q2W plus IV infusion of cetuximab 500 mg/m^2 on Day 1 then 500 mg/m^2 IV infusion Q2W starting on Day 15 up to 3 years until unacceptable toxicity, documentation of confirmed PD, or documentation of subject withdrawal for another reason. | Drug: Monalizumab Participants will receive IV infusion of monalizumab as stated in arm description. Drug: Cetuximab Participants will receive IV infusion of cetuximab as stated in arm description. |
