A Phase 1/2 interventional study of Monalizumab and Durvalumab in Advanced Solid Tumors, sponsored by MedImmune LLC. Active, not recruiting at 49 sites in 11 countries. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-06-15.
Sponsored by MedImmune LLC (part of AstraZeneca) · Phase 1/2, Interventional, and Treatment
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).
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.
4,040 studies on the registry are indexed under Neoplasm Metastasis; 886 are open to participants now.
This study's enrollment of 383 is above the median of 50 across 3,268 interventional studies indexed under Neoplasm Metastasis.
Browse Neoplasm Metastasis studies →MedImmune LLC is the lead sponsor of 270 studies on the registry; none are open to participants now.
Of its 52 completed or terminated interventional studies of FDA-regulated products, 29 (56%) have results posted.
First submitted after MedImmune LLC became part of AstraZeneca.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 · Drug: Durvalumab
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 · Drug: Durvalumab
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 · Drug: Durvalumab
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 · Drug: Durvalumab
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 · Drug: Durvalumab
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 · Drug: Durvalumab
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 · Drug: Durvalumab
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 · Drug: Durvalumab
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 · Drug: Durvalumab
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 · Drug: Durvalumab · Drug: mFOLFOX6 · Drug: Bevacizumab
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 · Drug: Durvalumab · Drug: Cetuximab · Drug: mFOLFOX6
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 · Drug: Durvalumab · Drug: Cetuximab
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 · Drug: Cetuximab
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 · Drug: Durvalumab · Drug: Cetuximab
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 · Drug: Cetuximab
Participants will receive IV infusion of monalizumab as stated in arm description.
Participants will receive IV infusion of durvalumab as stated in arm description.
Participants will receive IV infusion of cetuximab as stated in arm description.
Participants will receive IV infusion of mFOLFOX as stated in arm description.
Participants will receive IV infusion of bevacizumab as stated in arm description.
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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
Number of participants with at least 2-Grade shift from baseline in laboratory parameters are reported.
Time frame: 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).
Time frame: 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.
Time frame: Baseline (Days -28 to -1) through 54.8 months (maximum observed duration)
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.
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
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.
Time frame: 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).
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)
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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
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)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
Serum concentration of cetuximab is reported.
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
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.
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
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.
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
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.
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
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.
Time frame: 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.
Time frame: Screening (Days -28 to -1)
| Milestone | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 3 | 3 | 3 | 18 | 18 | 40 | 40 | 40 | 20 | 18 | 18 | 40 | 41 | 44 | 37 |
| Treated | 3 | 3 | 3 | 18 | 18 | 40 | 40 | 40 | 20 | 18 | 18 | 39 | 41 | 44 | 37 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 3 | 3 | 3 | 18 | 18 | 40 | 40 | 40 | 20 | 18 | 18 | 40 | 41 | 44 | 37 |
| Withdrew: Death | 1 | 3 | 0 | 16 | 14 | 29 | 34 | 28 | 19 | 10 | 8 | 29 | 29 | 29 | 27 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 0 | 1 | 1 | 2 | 2 | 0 | 2 | 0 | 3 | 3 | 2 | 0 |
| Withdrew: Withdrawal by subject | 2 | 0 | 2 | 2 | 2 | 7 | 2 | 7 | 1 | 1 | 2 | 4 | 4 | 4 | 2 |
| Withdrew: Un-specified | 0 | 0 | 0 | 0 | 1 | 3 | 2 | 3 | 0 | 5 | 8 | 4 | 5 | 9 | 8 |
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).
| Participants | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Any TEAEs | 3 | 3 | 3 | 18 | 17 | 39 | 40 | 39 | 20 | 18 | 18 | 39 | 41 | 44 | 36 |
| Any TESAEs | 1 | 0 | 1 | 8 | 4 | 11 | 16 | 17 | 7 | 10 | 11 | 10 | 5 | 9 | 11 |
Change from baseline in SBP and DBP (minimum post baseline change \[PBC\] and maximum PBC) are reported.
| mmHg | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SBP min PBC | -19.00 ± 21.63 | -26.00 ± 10.82 | -14.67 ± 11.55 | -22.94 ± 12.73 | -23.06 ± 20.48 | -21.45 ± 12.89 | -22.55 ± 13.35 | -21.23 ± 12.29 | -26.40 ± 12.75 | -29.28 ± 19.19 | -24.61 ± 10.92 | -23.31 ± 12.88 | -20.80 ± 11.87 | -25.57 ± 13.99 | -25.05 ± 16.86 |
| SBP max PBC | 27.33 ± 5.69 | 19.00 ± 5.57 | 28.67 ± 20.82 | 29.22 ± 15.78 | 22.00 ± 19.16 | 21.10 ± 12.04 | 22.15 ± 17.39 | 23.55 ± 14.13 | 22.95 ± 11.69 | 27.17 ± 21.63 | 23.61 ± 11.27 | 20.74 ± 15.31 | 17.20 ± 10.51 | 23.00 ± 13.18 | 22.59 ± 15.69 |
| DBP min PBC | -15.67 ± 18.01 | -22.00 ± 10.00 | -10.67 ± 9.07 | -17.89 ± 9.58 | -18.61 ± 11.05 | -16.60 ± 10.40 | -17.60 ± 9.81 | -13.05 ± 7.21 | -19.15 ± 10.28 | -18.11 ± 8.98 | -20.50 ± 9.79 | -16.13 ± 9.33 | -16.39 ± 9.94 | -18.09 ± 9.69 | -17.68 ± 12.15 |
| DBP max PBC | 23.67 ± 11.93 | 11.67 ± 4.93 | 18.00 ± 9.64 | 14.06 ± 12.75 | 12.39 ± 9.30 | 15.58 ± 9.69 | 12.63 ± 11.11 | 19.83 ± 10.15 | 16.65 ± 9.46 | 18.11 ± 9.33 | 14.22 ± 12.18 | 13.54 ± 10.01 | 13.10 ± 8.98 | 16.05 ± 10.06 | 14.43 ± 9.01 |
Change from baseline in RR (minimum PBC and maximum PBC) are reported.
| breaths/min | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| RR min PBC | -2.00 ± 2.00 | -3.00 ± 1.00 | -1.33 ± 2.31 | -1.78 ± 1.31 | -1.50 ± 1.86 | -1.93 ± 1.86 | -1.53 ± 1.52 | -1.83 ± 1.62 | -1.55 ± 3.12 | -2.00 ± 1.94 | -1.67 ± 1.78 | -2.15 ± 2.23 | -1.59 ± 1.52 | -2.00 ± 1.33 | -1.92 ± 1.89 |
| RR max PBC | 2.00 ± 3.46 | 2.33 ± 0.58 | 2.67 ± 1.15 | 1.72 ± 1.49 | 1.83 ± 1.42 | 2.40 ± 2.37 | 2.53 ± 2.24 | 2.40 ± 2.62 | 4.05 ± 3.09 | 2.50 ± 2.09 | 3.39 ± 3.62 | 1.85 ± 1.73 | 2.00 ± 1.55 | 2.59 ± 1.83 | 3.14 ± 4.60 |
Change from baseline in PR (minimum PBC and maximum PBC) are reported.
| beats/min | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PR min PBC | -5.33 ± 2.52 | -14.33 ± 6.51 | -7.00 ± 1.73 | -15.67 ± 11.83 | -15.39 ± 9.20 | -14.70 ± 9.39 | -12.24 ± 10.10 | -11.38 ± 10.98 | -13.95 ± 9.12 | -15.67 ± 8.84 | -18.11 ± 11.98 | -15.74 ± 11.20 | -13.15 ± 11.89 | -13.91 ± 7.04 | -11.68 ± 9.02 |
| PR max PBC | 38.33 ± 10.02 | 16.67 ± 6.11 | 21.67 ± 8.08 | 19.33 ± 15.05 | 17.78 ± 11.12 | 20.28 ± 10.03 | 20.68 ± 13.42 | 22.60 ± 12.17 | 25.80 ± 11.27 | 21.28 ± 13.48 | 21.06 ± 12.24 | 23.54 ± 12.83 | 23.88 ± 11.31 | 25.18 ± 13.71 | 27.38 ± 13.92 |
Change from baseline in BT (minimum PBC and maximum PBC) are reported.
| degree Celsius | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BT min PBC | -0.30 ± 0.30 | -0.37 ± 0.38 | -0.67 ± 0.55 | -0.66 ± 0.56 | -0.48 ± 0.28 | -0.62 ± 0.39 | -0.63 ± 0.42 | -0.47 ± 0.32 | -0.51 ± 0.26 | -0.84 ± 0.46 | -0.79 ± 0.48 | -0.51 ± 0.39 | -0.52 ± 0.33 | -0.65 ± 0.45 | -0.66 ± 0.58 |
| BT max PBC | 0.63 ± 0.32 | 0.93 ± 0.92 | 0.50 ± 0.26 | 0.78 ± 0.72 | 0.60 ± 0.73 | 0.65 ± 0.43 | 0.64 ± 0.46 | 0.77 ± 0.47 | 0.72 ± 0.46 | 0.89 ± 0.51 | 0.56 ± 0.43 | 0.75 ± 0.57 | 0.70 ± 0.53 | 0.91 ± 0.64 | 0.81 ± 0.66 |
Change from baseline in OS (minimum PBC and maximum PBC) are reported.
| Percentage of oxygen saturation | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OS min PBC | -1.00 ± NA | — | — | -3.00 ± NA | -3.00 ± NA | -0.67 ± 1.53 | -21.00 ± NA | — | 0 ± NA | 0.50 ± 2.12 | -4.00 ± NA | — | 0.50 ± 0.71 | -1.00 ± NA | -0.33 ± 2.80 |
| OS max PBC | -1.00 ± NA | — | — | -3.00 ± NA | -3.00 ± NA | -0.67 ± 1.53 | -21.00 ± NA | — | 0 ± NA | 0.50 ± 2.12 | -4.00 ± NA | — | 0.50 ± 0.71 | -1.00 ± NA | -0.33 ± 2.80 |
Participants who had notable QTcF and QTcB interval change from baseline are reported.
| Participants | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| QTcF>30 msec | 0 | 0 | 0 | 2 | 1 | 6 | 5 | 2 | 2 | 1 | 2 | 3 | 3 | 5 | 5 |
| QTcF>60 msec | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 |
| QTcB>30 msec | 1 | 0 | 0 | 3 | 2 | 5 | 5 | 4 | 3 | 1 | 6 | 4 | 8 | 9 | 6 |
| QTcB>60 msec | 0 | 0 | 0 | 1 | 0 | 1 | 3 | 1 | 1 | 0 | 0 | 1 | 2 | 0 | 1 |
Number of participants with at least 2-Grade shift from baseline in laboratory parameters are reported.
| Participants | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Anaemia | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 1 | 2 | 2 | 2 | 0 | 2 |
| White blood cell decreased | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 0 | 7 | 6 | 0 | 2 | 4 | 1 |
| Lymphocyte count decreased | 0 | 1 | 1 | 4 | 4 | 5 | 7 | 8 | 5 | 5 | 4 | 6 | 3 | 7 | 8 |
| Lymphocyte count increased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 |
| Neutrophil count decreased | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 9 | 11 | 0 | 1 | 1 | 1 |
| Platelet count decreased | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | 2 | 1 | 0 | 0 | 3 |
| Hypoalbuminemia | 1 | 0 | 0 | 6 | 3 | 6 | 6 | 6 | 2 | 2 | 2 | 9 | 2 | 6 | 5 |
| Creatinine increased | 1 | 1 | 1 | 1 | 4 | 4 | 4 | 8 | 2 | 4 | 2 | 0 | 0 | 0 | 0 |
| Gamma Glutamyl Transferase increased | 0 | 0 | 0 | 1 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hyponatremia | 1 | 0 | 1 | 2 | 3 | 3 | 5 | 5 | 1 | 4 | 2 | 0 | 0 | 0 | 0 |
| Hyperglycemia | 0 | 0 | 0 | 0 | 0 | 3 | 4 | 3 | 5 | 1 | 5 | 0 | 0 | 0 | 0 |
| Serum amylase increased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 6 | 0 | 0 | 0 | 0 |
| Aspartate aminotransferase increased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 0 |
| Blood bilirubin increased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 7 | 7 | 3 | 6 |
| Lipase increased | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 10 | 5 | 6 | 7 | 5 |
| Hypertriglyceridemia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 0 | 0 | 0 | 0 |
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).
| Participants | 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 |
|---|---|---|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | 0 | 0 | 0 | 0 | 0 |
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.
| Percentage of Participants | Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W | Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W |
|---|---|---|
| Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B | 0 (0.0 to 10.3) | 0 (0.0 to 9.0) |
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.
| Percentage of Participants | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Percentage of Participants With OR | 0 (0.0 to 70.8) | 0 (0.0 to 70.8) | 0 (0.0 to 84.2) | 0 (0.0 to 19.5) | 0 (0.0 to 19.5) | 7.5 (1.6 to 20.4) | 5.0 (0.7 to 18.2) | 0 (0.0 to 9.5) | 10.0 (1.2 to 31.7) | 44.4 (23.0 to 72.2) | 72.2 (46.5 to 90.3) |
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.
| Percentage of Participants | Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W | Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W |
|---|---|---|
| Percentage of Participants With OR in Exploration Cohorts C2A and C2B | 11.4 (4.0 to 25.6) | 5.4 (0.7 to 18.7) |
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).
| Percentage of Participants | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| DCR16 | 0 (0.0 to 70.8) | 33.3 (0.8 to 90.6) | 0 (0.0 to 70.8) | 22.2 (6.4 to 47.6) | 27.8 (9.7 to 53.5) | 30 (16.6 to 46.5) | 30 (16.6 to 46.5) | 25 (12.7 to 41.2) | 40 (19.1 to 63.9) | 77.8 (52.4 to 93.6) | 88.9 (65.3 to 98.6) |
| DCR24 | 0 (0.0 to 70.8) | 0 (0.0 to 70.8) | 0 (0.0 to 70.8) | 0 (0.0 to 18.5) | 11.1 (1.4 to 34.7) | 17.5 (7.3 to 32.8) | 15 (5.7 to 29.8) | 12.5 (4.2 to 26.8) | 25 (8.7 to 49.1) | 66.7 (41.0 to 86.7) | 77.8 (52.4 to 93.6) |
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).
| Percentage of Participants | 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 |
|---|---|---|---|---|
| DCR16 | 17.5 (7.3 to 32.8) | 34.1 (20.1 to 50.6) | 59.1 (43.2 to 73.7) | 56.8 (39.5 to 72.9) |
| DCR24 | 10.0 (2.8 to 23.7) | 7.3 (1.5 to 19.9) | 52.3 (36.7 to 67.5) | 45.9 (29.5 to 63.1) |
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.
| Weeks | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Duration of Response (DoR) | — | — | — | — | — | 16.1 (15.9 to NA) | 68.1 (24.0 to NA) | — | 22.9 (10.1 to NA) | 66.1 (16.1 to 85.4) | 72.3 (17.4 to NA) |
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.
| Weeks | 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 |
|---|---|---|---|---|
| DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B) | — | — | 32.1 (16.0 to NA) | 24.1 (12.1 to NA) |
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.
| Months | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Progression-Free Survival (PFS) | 1.8 (1.7 to NA) | 1.9 (1.8 to NA) | 1.9 (NA to NA) | 2.0 (1.7 to 3.4) | 1.8 (1.7 to 3.5) | 1.9 (1.8 to 3.6) | 1.8 (1.7 to 1.9) | 1.8 (1.7 to 3.3) | 1.9 (1.7 to 3.7) | 10.9 (5.7 to 17.7) | 14.7 (5.8 to 20.9) |
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.
| Months | 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 |
|---|---|---|---|---|
| Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B) | 1.8 (1.7 to 1.9) | 2.0 (1.7 to 3.3) | 5.3 (3.2 to 5.5) | 4.4 (2.1 to 5.5) |
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.
| Months | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Survival | 15.1 (NA to NA) | 20.1 (18.6 to NA) | NA (NA to NA) | 8.1 (4.0 to 16.7) | 13.4 (4.4 to 16.9) | 10.6 (6.0 to 20.1) | 16.7 (10.7 to 21.4) | 11.0 (6.7 to 17.3) | 8.8 (5.8 to 15.6) | 25.6 (13.8 to NA) | 29.6 (19.8 to NA) |
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.
| Months | 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 |
|---|---|---|---|---|
| Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B) | 10.3 (4.3 to 12.7) | 8.9 (6.8 to 11.3) | 14.6 (10.0 to 19.4) | 14.6 (7.2 to 18.7) |
Serum Cmax of monalizumab at pre-dose and end of infusion are reported.
| µg/mL | 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 + Dose-expansion: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W | Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Maximum Observed Serum Concentration (Cmax) of Monalizumab | 7.85 ± NA | 43.62 ± 12.54 | 144.88 ± NA | 315.74 ± 129.08 | 245.18 ± 142.35 | 304.48 ± 66.75 | 281.53 ± 155.57 | 346.85 ± 91.06 | 388.60 ± 194.64 | 289.25 ± 194.59 | 409.93 ± 175.43 |
Serum Cmin of monalizumab at pre-dose and end of infusion are reported.
| µg/mL | 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 + Dose-expansion: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W | Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Minimum Observed Serum Concentration (Cmin) of Monalizumab | 7.45 ± NA | 18.16 ± 6.70 | 92.55 ± NA | 145.04 ± 76.34 | 67.75 ± 57.82 | 141.39 ± 57.01 | 109.18 ± 45.54 | 129.59 ± 45.72 | 172.90 ± 84.55 | 148.05 ± 70.23 | 185.60 ± 105.68 |
Serum concentration of durvalumab is reported.
| µg/mL | Dose-escalation Cohorts(1-5)+Dose-expansion Cohorts+Dose-exploration Cohorts(A1,A2,C1A,C1B,C2A,C2B) |
|---|---|
| Week 1 Day 1 (PRE) | 0.100 ± 0.63 |
| Week 1 Day 1 (POST) | 399 ± 157 |
| Week 5 Day 1 (PRE) | 90.8 ± 95.0 |
| Week 9 Day 1 (PRE) | 127 ± 148 |
| Week 13 Day 1 (PRE) | 142 ± 123 |
| Week 13 Day 1 (POST) | 497 ± 277 |
| Week 25 Day 1 (PRE) | 149 ± 109 |
Serum concentration of cetuximab is reported.
| µg/mL | Exploration CohortsA2 (Mona+Durva+mFOLFOX6+Cetu), C1A, C2A (Mona+Durva+Cetu), C1B, C2B (Mona+Cetu) |
|---|---|
| Week 1 Day 1 (PRE) | 0.025 ± 0.00 |
| Week 1 Day 1 (POST) | 400 ± 138 |
| Week 5 Day 1 (PRE) | 73.6 ± 108.0 |
| Week 5 Day 1 (POST) | 344 ± 161 |
| Week 9 Day 1 (PRE) | 97.7 ± 137 |
| Week 13 Day 1 (PRE) | 61.7 ± 113 |
| Week 13 Day 1 (POST) | 387 ± 101 |
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.
| Participants | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Persistent Positive | 0 | 0 | 0 | 2 | 0 | 10 | 5 | 4 | 2 | 0 | 1 | 5 | 5 | 3 | 5 |
| Transient Positive | 0 | 0 | 0 | 1 | 0 | 1 | 2 | 1 | 2 | 0 | 0 | 1 | 1 | 2 | 0 |
| Treatment-boosted ADA | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment-emergent ADA | 0 | 0 | 0 | 3 | 0 | 11 | 7 | 5 | 4 | 0 | 1 | 6 | 6 | 5 | 5 |
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.
| Participants | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Persistent Positive | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Transient Positive | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment-boosted ADA | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Treatment-emergent ADA | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
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.
| Participants | Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab 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 |
|---|---|---|---|---|---|
| Persistent Positive | 0 | 1 | 0 | 0 | 0 |
| Transient Positive | 0 | 0 | 0 | 0 | 0 |
| Treatment-boosted ADA | 0 | 0 | 0 | 0 | 0 |
| Treatment-emergent ADA | 0 | 1 | 0 | 0 | 0 |
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.
| Participants | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TC>=25% | 0 | 0 | 0 | 2 | 1 | 0 | 5 | 1 | 6 | 0 | 0 | 0 | 1 | 1 | 0 |
| TC<25% | 3 | 3 | 3 | 11 | 13 | 29 | 32 | 31 | 10 | 16 | 18 | 31 | 32 | 35 | 32 |
| TC>=1% | 1 | 1 | 1 | 6 | 2 | 5 | 22 | 16 | 8 | 3 | 0 | 5 | 7 | 7 | 5 |
| TC<1% | 2 | 2 | 2 | 7 | 12 | 24 | 15 | 16 | 8 | 13 | 18 | 26 | 26 | 29 | 27 |
The HLA-E expression in pre-treatment tumor biopsies is reported.
| Participants | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HLA-E Carcinoma | 3 | 3 | 3 | 12 | 13 | 28 | 36 | 32 | 16 | 16 | 17 | 30 | 33 | 34 | 32 |
| HLA-E Lymphocyte | 3 | 3 | 3 | 12 | 13 | 30 | 37 | 32 | 17 | 16 | 17 | 29 | 32 | 34 | 32 |
| HLA-E Endothelium | 3 | 3 | 3 | 13 | 13 | 30 | 37 | 33 | 17 | 16 | 17 | 30 | 31 | 34 | 32 |
Collected over Day 1 through 246.9 weeks (maximum observed duration). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dose-escalation Cohort 1: Monalizumab 22.5 mg Q2W + Durvalumab 1500 mg Q4W | 1/3 (33.3%) | 1/3 (33.3%) | 3/3 (100%) |
| Dose-escalation Cohort 2: Monalizumab 75 mg Q2W + Durvalumab 1500 mg Q4W | 3/3 (100%) | 0/3 (0%) | 3/3 (100%) |
| Dose-escalation Cohort 3: Monalizumab 225 mg Q2W + Durvalumab 1500 mg Q4W | 0/3 (0%) | 1/3 (33.3%) | 3/3 (100%) |
| Dose-escalation Cohort 4: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W | 16/18 (88.9%) | 8/18 (44.4%) | 18/18 (100%) |
| Dose-escalation Cohort 5: Monalizumab 750 mg Q4W + Durvalumab 1500 mg Q4W | 14/18 (77.8%) | 4/18 (22.2%) | 16/18 (88.9%) |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (MSS-CRC) | 29/40 (72.5%) | 11/40 (27.5%) | 39/40 (97.5%) |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | 34/40 (85%) | 16/40 (40%) | 40/40 (100%) |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | 28/40 (70%) | 17/40 (42.5%) | 39/40 (97.5%) |
| Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 19/20 (95%) | 7/20 (35%) | 20/20 (100%) |
| Exploration Cohort A1: Monalizumab 750 mg Q2W+Durvalumab 1500 mg Q4W+mFOLFOX6 Q2W+Bevacizumab Q2W | 10/18 (55.6%) | 10/18 (55.6%) | 18/18 (100%) |
| Exploration CohortA2: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + mFOLFOX6 Q2W + Cetuximab Q2W | 8/18 (44.4%) | 11/18 (61.1%) | 18/18 (100%) |
| Exploration Cohort C1A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W | 29/40 (72.5%) | 10/39 (25.6%) | 39/39 (100%) |
| Exploration Cohort C1B: Monalizumab 750 mg Q2W + Cetuximab Q2W | 29/41 (70.7%) | 5/41 (12.2%) | 41/41 (100%) |
| Exploration Cohort C2A: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W + Cetuximab Q2W | 29/44 (65.9%) | 9/44 (20.5%) | 44/44 (100%) |
| Exploration Cohort C2B: Monalizumab 750 mg Q2W + Cetuximab Q2W | 27/37 (73%) | 11/37 (29.7%) | 36/37 (97.3%) |
| Event | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HydronephrosisRenal and urinary disorders | 0/3 | 0/3 | 1/3 | 2/18 | 0/18 | 1/40 | 0/40 | 1/40 | 0/20 | 0/18 | 0/18 | 0/39 | 0/41 | 0/44 | 0/37 |
| Abdominal painGastrointestinal disorders | 0/3 | 0/3 | 1/3 | 0/18 | 0/18 | 1/40 | 1/40 | 2/40 | 0/20 | 0/18 | 0/18 | 1/39 | 0/41 | 1/44 | 3/37 |
| AscitesGastrointestinal disorders | 0/3 | 0/3 | 1/3 | 0/18 | 0/18 | 1/40 | 1/40 | 1/40 | 0/20 | 0/18 | 0/18 | 1/39 | 0/41 | 0/44 | 0/37 |
| HaematocheziaGastrointestinal disorders | 1/3 | 0/3 | 0/3 | 0/18 | 0/18 | 0/40 | 0/40 | 0/40 | 0/20 | 0/18 | 0/18 | 0/39 | 0/41 | 0/44 | 0/37 |
| SepsisInfections and infestations | 0/3 | 0/3 | 0/3 | 0/18 | 0/18 | 1/40 | 0/40 | 0/40 | 1/20 | 1/18 | 3/18 | 0/39 | 0/41 | 1/44 | 2/37 |
| Small intestinal obstructionGastrointestinal disorders | 0/3 | 0/3 | 0/3 | 0/18 | 0/18 | 1/40 | 3/40 | 1/40 | 0/20 | 2/18 | 0/18 | 2/39 | 1/41 | 1/44 | 0/37 |
| PyrexiaGeneral disorders | 0/3 | 0/3 | 0/3 | 2/18 | 1/18 | 0/40 | 1/40 | 1/40 | 0/20 | 0/18 | 1/18 | 1/39 | 0/41 | 0/44 | 0/37 |
| Urinary tract infectionInfections and infestations | 0/3 | 0/3 | 0/3 | 2/18 | 0/18 | 0/40 | 0/40 | 0/40 | 0/20 | 0/18 | 0/18 | 0/39 | 1/41 | 0/44 | 0/37 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/3 | 0/3 | 0/3 | 0/18 | 0/18 | 0/40 | 0/40 | 0/40 | 0/20 | 2/18 | 1/18 | 0/39 | 0/41 | 0/44 | 0/37 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 0/3 | 0/3 | 0/3 | 2/18 | 0/18 | 1/40 | 0/40 | 2/40 | 0/20 | 0/18 | 0/18 | 0/39 | 0/41 | 0/44 | 0/37 |
| Event | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 3/3 | 1/3 | 1/3 | 5/18 | 2/18 | 6/40 | 10/40 | 10/40 | 6/20 | 8/18 | 6/18 | 5/39 | 5/41 | 9/44 | 7/37 |
| FatigueGeneral disorders | 2/3 | 1/3 | 2/3 | 2/18 | 4/18 | 7/40 | 11/40 | 20/40 | 1/20 | 14/18 | 7/18 | 14/39 | 8/41 | 11/44 | 6/37 |
| NauseaGastrointestinal disorders | 2/3 | 1/3 | 0/3 | 4/18 | 4/18 | 9/40 | 13/40 | 16/40 | 3/20 | 12/18 | 10/18 | 9/39 | 8/41 | 8/44 | 7/37 |
| Decreased appetiteMetabolism and nutrition disorders | 2/3 | 0/3 | 1/3 | 4/18 | 4/18 | 7/40 | 5/40 | 14/40 | 3/20 | 8/18 | 5/18 | 10/39 | 5/41 | 9/44 | 5/37 |
| Tumour painNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/3 | 0/3 | 0/3 | 0/18 | 0/18 | 0/40 | 0/40 | 1/40 | 0/20 | 0/18 | 0/18 | 1/39 | 1/41 | 1/44 | 0/37 |
| Dermatitis acneiformSkin and subcutaneous tissue disorders | 0/3 | 0/3 | 0/3 | 0/18 | 1/18 | 2/40 | 0/40 | 2/40 | 0/20 | 1/18 | 8/18 | 20/39 | 24/41 | 28/44 | 23/37 |
| Neuropathy peripheralNervous system disorders | 0/3 | 0/3 | 0/3 | 0/18 | 0/18 | 1/40 | 1/40 | 1/40 | 0/20 | 10/18 | 11/18 | 1/39 | 1/41 | 1/44 | 1/37 |
| AstheniaGeneral disorders | 0/3 | 0/3 | 0/3 | 3/18 | 5/18 | 2/40 | 12/40 | 2/40 | 10/20 | 1/18 | 1/18 | 2/39 | 3/41 | 0/44 | 4/37 |
| Lipase increasedInvestigations | 0/3 | 1/3 | 0/3 | 0/18 | 0/18 | 2/40 | 0/40 | 0/40 | 1/20 | 4/18 | 9/18 | 2/39 | 3/41 | 8/44 | 6/37 |
| RashSkin and subcutaneous tissue disorders | 0/3 | 1/3 | 1/3 | 0/18 | 4/18 | 5/40 | 3/40 | 3/40 | 1/20 | 3/18 | 9/18 | 12/39 | 8/41 | 5/44 | 9/37 |
Intent-to-treat (ITT) population included participants who were randomized and were analyzed according to the treatment group they were randomized to.
| Age, Continuous(Years) | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 58 ± 21.7 | 55.7 ± 18.0 | 59 ± 15.1 | 56.4 ± 13.5 | 60 ± 13.5 | 53.6 ± 12.9 | 61.5 ± 9.1 | 63.7 ± 8.5 | 63.2 ± 7.9 | 60.8 ± 9.9 | 55.4 ± 9.4 | 55.8 ± 10.7 | 52.3 ± 10.6 | 55.9 ± 11.3 | 58.8 ± 9.6 | 57.8 ± 11.2 |
| Sex: Female, Male(Participants) | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 3 | 3 | 2 | 17 | 6 | 15 | 40 | 40 | 6 | 8 | 8 | 17 | 16 | 17 | 18 | 216 |
| Male | 0 | 0 | 1 | 1 | 12 | 25 | 0 | 0 | 14 | 10 | 10 | 23 | 25 | 27 | 19 | 167 |
| Ethnicity (NIH/OMB)(Participants) | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 0 | 3 | 0 | 6 | 5 | 3 | 2 | 1 | 1 | 3 | 6 | 4 | 0 | 36 |
| Not Hispanic or Latino | 2 | 2 | 3 | 15 | 17 | 34 | 35 | 37 | 16 | 17 | 17 | 37 | 35 | 40 | 37 | 344 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Race (NIH/OMB)(Participants) | 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 (MSS-CRC) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Ovarian) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (Endometrial MSS) | Dose-expansion Cohort: Monalizumab 750 mg Q2W + Durvalumab 1500 mg Q4W (NSCLC) | 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 | 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 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Asian | 0 | 0 | 0 | 1 | 2 | 3 | 1 | 2 | 0 | 1 | 4 | 9 | 8 | 14 | 13 | 58 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 3 |
| Black or African American | 0 | 0 | 0 | 1 | 0 | 1 | 3 | 4 | 1 | 2 | 0 | 2 | 1 | 1 | 1 | 17 |
| White | 3 | 3 | 3 | 15 | 15 | 36 | 35 | 30 | 16 | 13 | 13 | 29 | 30 | 25 | 22 | 288 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 3 | 2 | 2 | 1 | 0 | 2 | 2 | 1 | 15 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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
Supporting information: Study protocol, Statistical analysis plan
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
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
Data sharing details ↗ · astrazenecagroup-dt.pharmacm.com
Ran from Feb 2016 to primary completion in Oct 2021, 68 months.
Results were first posted in Mar 2023, 1 year 4 months after primary completion.
Of 127 industry-sponsored phase 1/2 interventional studies under Neoplasm Metastasis, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 89. This study's 68 months is above that.
Counting every sponsor, half of 213 studies reached it within 62 months; a quarter within 41 and three quarters within 89.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in May 2026. You cannot join it, but the record below documents what was studied.
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