Advanced Solid TumorsPhase 1/2NCT02671435
A Study of Durvalumab (MEDI4736) and Monalizumab in Solid Tumors
A Phase 1/2 study testing Monalizumab, Durvalumab and Cetuximab in people with Advanced Solid Tumors, run by MedImmune LLC at 49 sites in 11 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- Monalizumab, Durvalumab and Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 383 participants
- Where
- 49 sitesin 11 countries
- Study dates
- 22 Feb 2016to 30 Jul 2027
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have histologic documentation of advanced recurrent or metastatic cancer.
- Participants must be at the recurrent/metastatic setting, with selected advanced solid tumors.
- Participants must have at least one lesion that is measurable by RECIST v1.1
- 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.
Who cannot join
- Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may be permitted upon discussion with the medical monitor.
- 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
- Receipt of any conventional or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.
Trial locations and contacts
49 sites in 11 countries.
49 sites in 11 countries
United States22 sites
Research Site
Aurora, Colorado, 80045
Research Site
Baltimore, Maryland, 21231
Research Site
Birmingham, Alabama, 35233
Research Site
Boston, Massachusetts, 02215
Research Site
Chicago, Illinois, 60611
Research Site
Dallas, Texas, 75235
Research Site
Detroit, Michigan, 48202
Research Site
Duarte, California, 91010
Research Site
La Jolla, California, 92093
Research Site
Los Angeles, California, 90089
Research Site
Nashville, Tennessee, 37203
Research Site
New Brunswick, New Jersey, 08903
Research Site
New Hyde Park, New York, 11042
Research Site
New York, New York, 10065
Research Site
Providence, Rhode Island, 02903
Research Site
Sacramento, California, 95817
Research Site
Salt Lake City, Utah, 84112
Research Site
San Antonio, Texas, 78229
Research Site
Santa Monica, California, 90404
Research Site
Scottsdale, Arizona, 85258
Research Site
Tampa, Florida, 33612
Research Site
The Bronx, New York, 10461
Spain6 sites
Research Site
Barcelona, 08035
Research Site
Madrid, 28027
Research Site
Madrid, 28034
Research Site
Málaga, 29010
Research Site
Pamplona, 31008
Research Site
Seville, 41013
South Korea5 sites
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Australia3 sites
Research Site
Blacktown, 2148
Research Site
Clayton, 3168
Research Site
Waratah, 2298
Belgium3 sites
Research Site
Brussels, 1200
Research Site
Edegem, 2650
Research Site
Leuven, 3000
Canada2 sites
Research Site
Toronto, Ontario, M5G 1Z5
Research Site
Vancouver, British Columbia, V5Z 4E6
United Kingdom2 sites
Research Site
London, SW2 6JJ
Research Site
Sutton, SM2 5PT
About this study
Official title: 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).
Read the 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.
- Conditions
- Advanced Solid Tumors
- Being tested
- Monalizumab, Durvalumab, Cetuximab, mFOLFOX6, Bevacizumab
- Keywords
- Colorectal, colon, CRC, solid tumors, check point inhibitors, immunotherapy, metastatic
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MonalizumabDrug
Participants will receive IV infusion of monalizumab as stated in arm description.
DurvalumabDrug
Participants will receive IV infusion of durvalumab as stated in arm description.
CetuximabDrug
Participants will receive IV infusion of cetuximab as stated in arm description.
mFOLFOX6Drug
Participants will receive IV infusion of mFOLFOX as stated in arm description.
BevacizumabDrug
Participants will receive IV infusion of bevacizumab as stated in arm description.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Monalizumab; Drug: Durvalumab |
| Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab |
| Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab |
| Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab |
| Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC) | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (ovarian) | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab |
| Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab; Drug: mFOLFOX6; Drug: Bevacizumab |
| Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab; Drug: Cetuximab; Drug: mFOLFOX6 |
| Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab; Drug: Cetuximab |
| Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Cetuximab |
| Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Durvalumab; Drug: Cetuximab |
| Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W | Experimental | 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. Receives: Drug: Monalizumab; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
Secondary outcomes (19)
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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Screening (Days -28 to -1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2016 (estimated)
- Study start22 Feb 2016
- Primary completion26 Oct 2021
- Study completion30 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 383 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02671435
- Sponsor's protocol ID
- D419NC00001
- Other IDs
- D419NC00001, 2016-000662-38, 2016
- Status last verified
- May 2026
- First submitted
- 28 Jan 2016
- Last updated
- 15 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: 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
Publications
Patel SP, Alonso-Gordoa T, Banerjee S, Wang D, Naidoo J, Standifer NE, Palmer DC, Cheng LY, Kourtesis P, Ascierto ML, Das M, Diamond JR, Hellmann MD, Carneiro BA. Phase 1/2 study of monalizumab plus durvalumab in patients with advanced solid tumors. J Immunother Cancer. 2024 Feb 2;12(2):e007340. doi: 10.1136/jitc-2023-007340.
PubMed 38309722Hwang M, Fan C, Yue MS, Zhou D, Paturel C, Andre P, Cheng LY, Mitchell P, Kourtesis P, Ruscica D, Das M, Morsli N, Ren S, Gibbs M, Phipps A, Song X. Population Pharmacokinetics of Monalizumab in Patients With Advanced Solid Tumors. J Clin Pharmacol. 2023 Jul;63(7):817-829. doi: 10.1002/jcph.2220. Epub 2023 Apr 10.
PubMed 36852723
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of Durvalumab and Monalizumab in Adult Subjects With Select Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02671435
- Acronym / sponsor ID
- D419NC00001
- Conditions
- Advanced Solid Tumors
- Keywords
- Colorectal, colon, CRC, solid tumors, check point inhibitors, immunotherapy, metastatic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 383 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 22 Feb 2016 (actual)
- Primary completion
- 26 Oct 2021 (actual)
- Study completion
- 30 Jul 2027 (estimated)
- First posted
- 2 Feb 2016 (estimated)
- Results
- Posted 9 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W | Experimental | Drug: Monalizumab, Drug: DurvalumabParticipants 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. |
| Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W | Experimental | Drug: Monalizumab, Drug: DurvalumabParticipants 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. |
| Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W | Experimental | Drug: Monalizumab, Drug: DurvalumabParticipants 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. |
| Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W | Experimental | Drug: Monalizumab, Drug: DurvalumabParticipants 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. |
| Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W | Experimental | Drug: Monalizumab, Drug: DurvalumabParticipants 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. |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC) | Experimental | Drug: Monalizumab, Drug: DurvalumabParticipants 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. |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (ovarian) | Experimental | Drug: Monalizumab, Drug: DurvalumabParticipants 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. |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Experimental | Drug: Monalizumab, Drug: DurvalumabParticipants 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. |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | Experimental | Drug: Monalizumab, Drug: DurvalumabParticipants 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. |
| Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W | Experimental | Drug: Monalizumab, Drug: Durvalumab, Drug: mFOLFOX6, Drug: BevacizumabParticipants 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. |
| Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W | Experimental | Drug: Monalizumab, Drug: Durvalumab, Drug: Cetuximab, Drug: mFOLFOX6Participants 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. |
| Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W | Experimental | Drug: Monalizumab, Drug: Durvalumab, Drug: CetuximabParticipants 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. |
| Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W | Experimental | Drug: Monalizumab, Drug: CetuximabParticipants 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. |
| Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W | Experimental | Drug: Monalizumab, Drug: Durvalumab, Drug: CetuximabParticipants 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. |
| Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W | Experimental | Drug: Monalizumab, Drug: CetuximabParticipants 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Participants must have histologic documentation of advanced recurrent or metastatic cancer.
- Participants must be at the recurrent/metastatic setting, with selected advanced solid tumors.
- Participants must have at least one lesion that is measurable by RECIST v1.1
- 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.
Key exclusion criteria (4 listed)
- Prior treatment with immunotherapy agents. Prior treatment with antitumor vaccines may be permitted upon discussion with the medical monitor.
- 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
- Receipt of any conventional or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MonalizumabParticipants will receive IV infusion of monalizumab as stated in arm description. | Drug | 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 |
| DurvalumabParticipants will receive IV infusion of durvalumab as stated in arm description. | Drug | 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 |
| CetuximabParticipants will receive IV infusion of cetuximab as stated in arm description. | Drug | 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 |
| mFOLFOX6Participants will receive IV infusion of mFOLFOX as stated in arm description. | Drug | 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 |
| BevacizumabParticipants will receive IV infusion of bevacizumab as stated in arm description. | Drug | Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: Day 1 through 246.9 weeks (maximum observed duration)
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).
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in SBP and DBP (minimum post baseline change [PBC] and maximum PBC) are reported.
Change From Baseline in Respiratory Rate (RR)
Time frame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in RR (minimum PBC and maximum PBC) are reported.
Change From Baseline in Pulse Rate (PR)
Time frame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in PR (minimum PBC and maximum PBC) are reported.
Change From Baseline in Body Temperature (BT)
Time frame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in BT (minimum PBC and maximum PBC) are reported.
Change From Baseline in Oxygen Saturation (OS)
Time frame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Change from baseline in OS (minimum PBC and maximum PBC) are reported.
Number of Participants With Notable Change in QTcF and QTcB From Baseline
Time frame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Participants who had notable QTcF and QTcB interval change from baseline are reported.
Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters
Time frame: Day 1 (baseline) through 246.9 weeks (maximum observed duration)
Number of participants with at least 2-Grade shift from baseline in laboratory parameters are reported.
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: From Day 1 to 28 days after the first dose of study drugs
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).
Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B
Time frame: Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
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.
19 secondary outcomes
Percentage of Participants With OR
Time frame: Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
Percentage of Participants With OR in Exploration Cohorts C2A and C2B
Time frame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Percentage of Participants With Disease Control (DC)
Time frame: 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)
Time frame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Duration of Response (DoR)
Time frame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B)
Time frame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Progression-Free Survival (PFS)
Time frame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B)
Time frame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Overall Survival
Time frame: Baseline (-28 to -1 day) through 54.8 months (maximum observed duration)
Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B)
Time frame: Baseline (-28 to -1 day) through 54.8 weeks (maximum observed duration)
Maximum Observed Serum Concentration (Cmax) of Monalizumab
Time frame: Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions
Minimum Observed Serum Concentration (Cmin) of Monalizumab
Time frame: Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions
Serum Concentration of Durvalumab
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Screening (Days -28 to -1)
Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies
Time frame: Screening (Days -28 to -1)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38309722Patel SP, Alonso-Gordoa T, Banerjee S, Wang D, Naidoo J, Standifer NE, Palmer DC, Cheng LY, Kourtesis P, Ascierto ML, Das M, Diamond JR, Hellmann MD, Carneiro BA. Phase 1/2 study of monalizumab plus durvalumab in patients with advanced solid tumors. J Immunother Cancer. 2024 Feb 2;12(2):e007340. doi: 10.1136/jitc-2023-007340.
- Derived from this study: PubMed 36852723Hwang M, Fan C, Yue MS, Zhou D, Paturel C, Andre P, Cheng LY, Mitchell P, Kourtesis P, Ruscica D, Das M, Morsli N, Ren S, Gibbs M, Phipps A, Song X. Population Pharmacokinetics of Monalizumab in Patients With Advanced Solid Tumors. J Clin Pharmacol. 2023 Jul;63(7):817-829. doi: 10.1002/jcph.2220. Epub 2023 Apr 10.
- redacted CSPLink provided by the sponsor.
- redacted SAPLink provided by the sponsor.
- redacted CSR SynopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
49 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Monalizumab, Durvalumab and Cetuximab in people with Advanced Solid Tumors, run by MedImmune LLC at 49 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in United States, Spain, South Korea, Australia, Belgium and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) (time frame: Day 1 through 246.9 weeks (maximum observed duration)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02671435, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.