Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. Any TEAEs data is inclusive of both serious and other adverse events (non-serious). |
Day 1 through 246.9 weeks (maximum observed duration) |
|
| Primary |
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
Change from baseline in SBP and DBP (minimum post baseline change [PBC] and maximum PBC) are reported. |
Day 1 (baseline) through 246.9 weeks (maximum observed duration) |
|
| Primary |
Change From Baseline in Respiratory Rate (RR) |
Change from baseline in RR (minimum PBC and maximum PBC) are reported. |
Day 1 (baseline) through 246.9 weeks (maximum observed duration) |
|
| Primary |
Change From Baseline in Pulse Rate (PR) |
Change from baseline in PR (minimum PBC and maximum PBC) are reported. |
Day 1 (baseline) through 246.9 weeks (maximum observed duration) |
|
| Primary |
Change From Baseline in Body Temperature (BT) |
Change from baseline in BT (minimum PBC and maximum PBC) are reported. |
Day 1 (baseline) through 246.9 weeks (maximum observed duration) |
|
| Primary |
Change From Baseline in Oxygen Saturation (OS) |
Change from baseline in OS (minimum PBC and maximum PBC) are reported. |
Day 1 (baseline) through 246.9 weeks (maximum observed duration) |
|
| Primary |
Number of Participants With Notable Change in QTcF and QTcB From Baseline |
Participants who had notable QTcF and QTcB interval change from baseline are reported. |
Day 1 (baseline) through 246.9 weeks (maximum observed duration) |
|
| Primary |
Number of Participants With at Least 2-Grade Shift From Baseline in Laboratory Parameters |
Number of participants with at least 2-Grade shift from baseline in laboratory parameters are reported. |
Day 1 (baseline) through 246.9 weeks (maximum observed duration) |
|
| Primary |
Number of Participants With Dose Limiting Toxicities (DLTs) |
DLT: Any study drug related Grade (G) 3 or higher toxicity that occurred during DLT evaluation period including: any G>=3 noninfectious colitis/pneumonitis, liver transaminase elevation (TE) >=5 but =<8 upper limit of normal (ULN), any G4 immune-mediated AE (imAE)/immune-related AE (irAE), any G>=3 clinically significant non-hematologic toxicity, TE >8 ULN or total bilirubin (TBL) >5 ULN, increase in AST or ALT >=3 ULN along with TBL >=2 ULN, thrombocytopenia (G3/4 associated with G3/higher hemorrhage, G3 that did not improve by at least 1 grade within 7 days, and G4), G4 febrile neutropenia (FN), G3 FN of >=5 days and G3 FN regardless of duration, G4 neutropenia of >7 days, G3/4 neutropenia not associated with fever/systemic infection, and anemia (G3 and G4). |
From Day 1 to 28 days after the first dose of study drugs |
|
| Primary |
Percentage of Participants With Objective Response (OR) in Exploration Cohorts C1A and C1B |
The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST V 1.1) guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. |
Baseline (Days -28 to -1) through 54.8 months (maximum observed duration) |
|
| Secondary |
Percentage of Participants With OR |
The OR is defined as best overall response of CR or confirmed PR according to RECIST V 1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. |
Baseline (Days -28 to -1) through 54.8 months (maximum observed duration) |
|
| Secondary |
Percentage of Participants With OR in Exploration Cohorts C2A and C2B |
The OR is defined as best overall response of confirmed CR or confirmed PR according to RECIST V 1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. |
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration) |
|
| Secondary |
Percentage of Participants With Disease Control (DC) |
The DC is defined as best overall response of confirmed CR, confirmed PR, or stable disease (SD) based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. Participants with SD were included in the DC if they maintained SD for >= 8 weeks from start of treatment. The DCR16 and DCR24 are reported (participants with SD >= 16 weeks and >=24 weeks). |
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration) |
|
| Secondary |
Percentage of Participants With DC in Exploration Cohorts (C1A, C1B, C2A, and C2B) |
The DC is defined as best overall response of confirmed CR, confirmed PR, or SD based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. Participants with SD were included in the DC if they maintained SD for >= 8 weeks from start of treatment. The DCR16 and DCR24 are reported (participants with SD >= 16 weeks and >=24 weeks). |
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration) |
|
| Secondary |
Duration of Response (DoR) |
The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression (PD) based on RECIST v1.1 or death due to any cause, whichever occurred first. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The DoR was evaluated using Kaplan-Meier method. |
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration) |
|
| Secondary |
DoR in Exploration Cohorts (C1A, C1B, C2A, and C2B) |
The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level lesions. The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in between. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The DoR was evaluated using Kaplan-Meier method. |
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration) |
|
| Secondary |
Progression-Free Survival (PFS) |
The PFS is defined as the time from the start of study treatment until the first documentation of PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The PFS was estimated using Kaplan-Meier method. |
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration) |
|
| Secondary |
Progression-Free Survival (PFS) in Exploration Cohorts (C1A, C1B, C2A, and C2B) |
The PFS is defined as the time from the start of study treatment until the first documentation of PD based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions or unequivocal progression of existing non-target lesions, taking as reference the smallest sum on study and appearance of one or more new lesions. The PFS was estimated using Kaplan-Meier method. |
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration) |
|
| Secondary |
Overall Survival |
The overall survival is defined as the time from the start of study treatment until death due to any cause. The overall survival was estimated using Kaplan-Meier method. |
Baseline (-28 to -1 day) through 54.8 months (maximum observed duration) |
|
| Secondary |
Overall Survival in Exploration Cohorts (C1A, C1B, C2A, and C2B) |
The overall survival is defined as the time from the start of study treatment until death due to any cause. The overall survival was estimated using Kaplan-Meier method. |
Baseline (-28 to -1 day) through 54.8 weeks (maximum observed duration) |
|
| Secondary |
Maximum Observed Serum Concentration (Cmax) of Monalizumab |
Serum Cmax of monalizumab at pre-dose and end of infusion are reported. |
Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions |
|
| Secondary |
Minimum Observed Serum Concentration (Cmin) of Monalizumab |
Serum Cmin of monalizumab at pre-dose and end of infusion are reported. |
Day 85: Pre-dose and end of infusion (within 10 minutes) after cohort specific infusions |
|
| Secondary |
Serum Concentration of Durvalumab |
Serum concentration of durvalumab is reported. |
Pre-dose (PRE) on Day 1 of Weeks 1, 5, 9, 13, and 25 and post-dose (POST) on Day 1 of Weeks 1 and 13 |
|
| Secondary |
Serum Concentration of Cetuximab |
Serum concentration of cetuximab is reported. |
Pre-dose (PRE) on Day 1 of Weeks 1, 5, 9, and 13 and post-dose (POST) on Day 1 of Weeks 1, 5, and 13 |
|
| Secondary |
Number of Participants With Positive Anti-Drug Antibodies (ADA) to Monalizumab |
Number of participants with positive ADA to monalizumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher level following drug administration. Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA. |
Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab) |
|
| Secondary |
Number of Participants With Positive ADA to Durvalumab |
Number of participants with positive ADA to monalizumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher level following drug administration. Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA. |
Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 13, and 25, and 90 days after the last dose of monalizumab) |
|
| Secondary |
Number of Participants With Positive ADA to Cetuximab |
Number of participants with positive ADA to cetuximab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher level following drug administration. Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA. |
Day 1 through 54.8 months (Day 1 of Weeks 1, 5, 9 [if EOT occurred], and 13, and 30 days after the last dose of monalizumab) |
|
| Secondary |
Number of Participants With Programmed Death Ligand 1 (PD-L1) Expression in Pretreatment Tumor Biopsies |
Number of participants with PD-L1 expression in pre-treatment tumor biopsies is reported. The participants were stratified into four categories: tumor cells (TC) >= 25%, TC<25%, TC>=1%, and TC<1%, based on the historical use of PD-L1 cutoffs. |
Screening (Days -28 to -1) |
|
| Secondary |
Number of Participants With Human Leukocyte Antigen (HLA)-E Expression in Pretreatment Tumor Biopsies |
The HLA-E expression in pre-treatment tumor biopsies is reported. |
Screening (Days -28 to -1) |
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