Brief Summary

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 Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

383

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Feb 2016

Longer than P75 for phase_1

Geographic Reach

11 countries

49 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

9.5 years study duration

First Submitted

Initial submission to the registry

January 28, 2016

Completed

5 days until next milestone

First Posted

Study publicly available on registry

February 2, 2016

Completed

20 days until next milestone

Study Start

First participant enrolled

February 22, 2016

Completed

5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 26, 2021

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

March 9, 2023

Completed

2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2025

Completed

Last Updated

July 22, 2025

Status Verified

July 1, 2025

Enrollment Period

5.7 years

First QC Date

January 28, 2016

Results QC Date

October 21, 2022

Last Update Submit

July 18, 2025

Conditions

Advanced Solid Tumors

Keywords

Colorectal, colon, CRC, solid tumors, check point inhibitors, immunotherapy, metastatic

Outcome Measures

Primary Outcomes (10)

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 Outcomes (19)

Percentage of Participants With OR
Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
Percentage of Participants With OR in Exploration Cohorts C2A and C2B
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Percentage of Participants With Disease Control (DC)
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)
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Duration of Response (DoR)
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
+14 more secondary outcomes

Study Arms (15)

Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W

EXPERIMENTAL

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.