A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors
Study identifier:D419NC00001
ClinicalTrials.gov identifier:NCT02671435
EudraCT identifier:N/A
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, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Monalizumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Durvalumab, Cetuximab, Cetuximab, Cetuximab, Cetuximab, Cetuximab, mFOLFOX6, mFOLFOX6, Bevacizumab
Sex
All
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: 29 Jun 2023
Study design
Allocation: Randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Verification:
Verified 01 Dec 2022 by MedImmune, LLC
Sponsors
MedImmune, LLC
Collaborators
-
Inclusion and exclusion criteria
Loading...
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. |
