A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors

A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Monalizumab; Drug: Durvalumab; Drug: mFOLFOX6; Drug: Bevacizumab; Drug: Cetuximab

Detailed Description

The study consists of 3 parts: dose escalation (Part 1), dose expansion (Part 2), and dose exploration (Part 3). Part 1 will evaluate dose escalation of durvalumab in combination with monalizumab in adult participants with select advanced solid tumor malignancies. Part 2 will evaluate further the identified dose of durvalumab in combination with monalizumab from Part 1 in adult participants with select advanced solid tumor malignancies. Part 3 will evaluate dose exploration of durvalumab in combination with monalizumab and standard of care systemic therapy with or without biological agent, and monalizumab in combination with biological agent in adult participants with CRC.

• Study Type: Interventional
• Enrollment (Actual): 383
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Blacktown, Australia, 2148
    • Research Site
  • Clayton, Australia, 3168
    • Research Site
  • Waratah, Australia, 2298
    • Research Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Research Site
  • Edegem, Belgium, 2650
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Research Site
• France
  • Marseille CEDEX 5, France, 13385
    • Research Site
  • Nantes CEDEX 1, France, 44093
    • Research Site
• Hungary
  • Debrecen, Hungary, 4032
    • Research Site
• Italy
  • Milano, Italy, 20141
    • Research Site
  • Milano, Italy, 20132
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Seoul, Korea, Republic of, 06591
    • Research Site
• New Zealand
  • Grafton, New Zealand, 1023
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28027
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
• United Kingdom
  • London, United Kingdom, SW2 6JJ
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Research Site
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Research Site
  • California
    • Duarte, California, United States, 91010
      • Research Site
    • La Jolla, California, United States, 92093
      • Research Site
    • Los Angeles, California, United States, 90089
      • Research Site
    • Sacramento, California, United States, 95817
      • Research Site
    • Santa Monica, California, United States, 90404
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Research Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Research Site
  • New York
    • Bronx, New York, United States, 10461
      • Research Site
    • New Hyde Park, New York, United States, 11042
      • Research Site
    • New York, New York, United States, 10065
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75235
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: mFOLFOX6; Participants will receive IV infusion of mFOLFOX as stated in arm description.; Drug: Cetuximab; Participants will receive IV infusion of cetuximab 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (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. Any TEAEs data is inclusive of both serious and other adverse events (non-serious).	Day 1 through 246.9 weeks (maximum observed duration)
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Change from baseline in SBP and DBP (minimum post baseline change [PBC] and maximum PBC) are reported.	Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change From Baseline in Respiratory Rate (RR)	Change from baseline in RR (minimum PBC and maximum PBC) are reported.	Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change From Baseline in Pulse Rate (PR)	Change from baseline in PR (minimum PBC and maximum PBC) are reported.	Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change From Baseline in Body Temperature (BT)	Change from baseline in BT (minimum PBC and maximum PBC) are reported.	Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change From Baseline in Oxygen Saturation (OS)	Change from baseline in OS (minimum PBC and maximum PBC) are reported.	Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Number of Participants With Notable Change in QTcF and QTcB From Baseline	Participants who had notable QTcF and QTcB interval change from baseline are reported.	Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters	Number of participants with at least 2-Grade shift from baseline in laboratory parameters are reported.	Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Number of Participants With Dose Limiting Toxicities (DLTs)	DLT: Any study drug related Grade (G) 3 or higher toxicity that occurred during DLT evaluation period including: any G>=3 noninfectious colitis/pneumonitis, liver transaminase elevation (TE) >=5 but =<8 upper limit of normal (ULN), any G4 immune-mediated AE (imAE)/immune-related AE (irAE), any G>=3 clinically significant non-hematologic toxicity, TE >8 ULN or total bilirubin (TBL) >5 ULN, increase in AST or ALT >=3 ULN along with TBL >=2 ULN, thrombocytopenia (G3/4 associated with G3/higher hemorrhage, G3 that did not improve by at least 1 grade within 7 days, and G4), G4 febrile neutropenia (FN), G3 FN of >=5 days and G3 FN regardless of duration, G4 neutropenia of >7 days, G3/4 neutropenia not associated with fever/systemic infection, and anemia (G3 and G4).	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	The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST V 1.1) guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between.	Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With OR	The OR is defined as best overall response of CR or confirmed PR according to RECIST V 1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between.	Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
Percentage of Participants With OR in Exploration Cohorts C2A and C2B	The OR is defined as best overall response of confirmed CR or confirmed PR according to RECIST V 1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between.	Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Percentage of Participants With Disease Control (DC)	The DC is defined as best overall response of confirmed CR, confirmed PR, or stable disease (SD) based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days 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. Participants with SD were included in the DC if they maintained SD for >= 8 weeks from start of treatment. The DCR16 and DCR24 are reported (participants with SD >= 16 weeks and >=24 weeks).	Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Percentage of Participants With DC in Exploration Cohorts (C1A, C1B, C2A, and C2B)	The DC is defined as best overall response of confirmed CR, confirmed PR, or SD based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days 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. Participants with SD were included in the DC if they maintained SD for >= 8 weeks from start of treatment. The DCR16 and DCR24 are reported (participants with SD >= 16 weeks and >=24 weeks).	Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Duration of Response (DoR)	The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression (PD) based on RECIST v1.1 or death due to any cause, whichever occurred first. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The DoR was evaluated using Kaplan-Meier method.	Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B)	The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The DoR was evaluated using Kaplan-Meier method.	Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Progression-Free Survival (PFS)	The PFS is defined as the time from the start of study treatment until the first documentation of PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The PFS was estimated using Kaplan-Meier method.	Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B)	The PFS is defined as the time from the start of study treatment until the first documentation of PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The PFS was estimated using Kaplan-Meier method.	Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Overall Survival	The overall survival is defined as the time from the start of study treatment until death due to any cause. The overall survival was estimated using Kaplan-Meier method.	Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B)	The overall survival is defined as the time from the start of study treatment until death due to any cause. The overall survival was estimated using Kaplan-Meier method.	Baseline (-28 to -1 day) through 54.8 weeks (maximum observed duration)
Maximum Observed Serum Concentration (Cmax) of Monalizumab	Serum Cmax of monalizumab at pre-dose and end of infusion are reported.	Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions
Minimum Observed Serum Concentration (Cmin) of Monalizumab	Serum Cmin of monalizumab at pre-dose and end of infusion are reported.	Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions
Serum Concentration of Durvalumab	Serum concentration of durvalumab is reported.	Pre-dose (PRE) on Day 1 of Weeks 1, 5, 9, 13, and 25 and post-dose (POST) on Day 1 of Weeks 1 and 13
Serum Concentration of Cetuximab	Serum concentration of cetuximab is reported.	Pre-dose (PRE) on Day 1 of Weeks 1, 5, 9, and 13 and post-dose (POST) on Day 1 of Weeks 1, 5, and 13
Number of Participants With Positive Anti-Drug Antibodies (ADA) to Monalizumab	Number of participants with positive ADA to monalizumab 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). Treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher level following drug administration. Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA.	Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab)
Number of Participants With Positive ADA to Durvalumab	Number of participants with positive ADA to monalizumab 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). Treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher level following drug administration. Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA.	Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab)
Number of Participants With Positive ADA to Cetuximab	Number of participants with positive ADA to cetuximab 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). Treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher level following drug administration. Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA.	Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 9 [if EOT occurred], and 13, and 30 days after the last dose of monalizumab)
Number of Participants With Programmed Death Ligand 1 (PD-L1) Expression in Pretreatment Tumor Biopsies	Number of participants with PD-L1 expression in pre-treatment tumor biopsies is reported. The participants were stratified into four categories: tumor cells (TC) >= 25%, TC<25%, TC>=1%, and TC<1%, based on the historical use of PD-L1 cutoffs.	Screening (Days -28 to -1)
Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies	The HLA-E expression in pre-treatment tumor biopsies is reported.	Screening (Days -28 to -1)

Collaborators and Investigators

• Sponsor: MedImmune LLC

Publications and helpful links

Helpful Links

• redacted CSP
• redacted SAP
• redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2016
• Primary Completion (Actual): October 26, 2021
• Study Completion (Estimated): September 2, 2024

Study Registration Dates

• First Submitted: January 28, 2016
• First Submitted That Met QC Criteria: January 28, 2016
• First Posted (Estimated): February 2, 2016

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Colorectal, colon, CRC, solid tumors, check point inhibitors, immunotherapy, metastatic
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Durvalumab; Bevacizumab; Cetuximab
• Other Study ID Numbers: D419NC00001 (Other Grant/Funding Number: Medimmune LLC); 2016-000662-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP