Head and Neck Cancer
Conditions
Brief summary
A study in patients with metastatic or recurrent squamous cell cancer of the head and neck to evaluate the effectiveness of Nivolumab plus Ipilumumab vs. Nivolumab alone (CheckMate 714)
Interventions
BIOLOGICALNivolumab
BIOLOGICALIpilimumab
OTHERPlacebo
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed squamous cell head and neck cancer * Widespread (metastatic) disease, or returned after previous treatment (recurrent) * Tumor sample must be available for analysis of PDL1 (Programmed death-ligand 1) and HPV \[Human Papilloma Virus (oropharynx only)\] * Performance status ECOG 0-1 (Eastern Cooperative Oncology Group)
Exclusion criteria
* Previous treatment for metastatic or recurrent disease * Cancer arising from one of the following primary sites: paranasal sinus, nasopharynx, salivary gland, skin * Any non-squamous subtype * Active autoimmune disease * Positive test for hepatitis B, C or HIV (Human Immunodeficiency Virus) virus * Previous treatment with checkpoint inhibitor drugs * Active CNS metastases or carcinomatous meningitis Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | Approximately up to 30 months (from FPFV to Data base lock) | ORR is defined as best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | Approximately up to 30 months (from FPFV to Data base lock) | The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. |
| Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | Approximately up to 30 months (from FPFV to Data base lock) | Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup | From randomization to disease progression or death. Approximately 63 Months | the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Overall Survival (OS) | From randomization to death. Approximately 63 Months | Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. |
| Overall Survival (OS) - Platinum Refractory Subgroup | From randomization to death. Approximately 63 Months | Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. |
| Overall Survival (OS) - Platinum Eligible Subgroup | From randomization to death. Approximately 63 Months | Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. |
| Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status | From randomization to death. Approximately 63 Months | Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. |
| ORR - Platinum Eligible Subgroup Based on HPV p-16 Status | From randomization to end of study. Approximately 63 Months | ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | From randomization to end of study. Approximately 63 Months | ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| ORR - Platinum Refractory Subgroup Based on HPV p-16 Status | From randomization to end of study. Approximately 63 Months | ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | From randomization to end of study. Approximately 63 Months | ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Duration of Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status | From randomization to disease progression or death. Approximately 63 Months | The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. |
| Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | From randomization to disease progression or death. Approximately 63 Months | The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb |
| Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status | From randomization to disease progression or death. Approximately 63 Months | the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | From randomization to disease progression or death. Approximately 63 Months | the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status | From randomization to death. Approximately 63 Months | Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. |
| Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup | From randomization to end of study. Approximately 63 Months | ORR is defined as percentage of participants with a complete response (CR) or partial response (PR). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | From randomization to death. Approximately 63 Months | Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb |
| Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | From randomization to disease progression or death. Approximately 63 Months | the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status | From randomization to disease progression or death. Approximately 63 Months | the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status | From randomization to disease progression or death. Approximately 63 Months | The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | From randomization to disease progression or death. Approximately 63 Months | The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | From randomization to disease progression or death. Approximately 63 Months | The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | From randomization to end of study. Approximately 63 Months | ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | From randomization to death. Approximately 63 Months | Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay |
| Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | From randomization to disease progression or death. Approximately 63 Months | The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | From randomization to disease progression or death. Approximately 63 Months | The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | From randomization to end of study. Approximately 63 Months | ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | From randomization to death. Approximately 63 Months | Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay |
| Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | From randomization to disease progression or death. Approximately 63 Months | The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | From randomization to death. Approximately 63 Months | Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb |
| Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup | From randomization to disease progression or death. Approximately 63 Months | The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. |
| Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | From randomization to disease progression or death. Approximately 63 Months | The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
Countries
Argentina, Belgium, Brazil, Canada, Chile, Czechia, Finland, France, Ireland, Italy, Mexico, Netherlands, Norway, Romania, Russia, South Africa, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
425 randomized and 423 participants treated.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A - Platinum Refractory Subgroup Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy.
Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W | 159 |
| Treatment B - Platinum Refractory Subgroup Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy.
Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W | 82 |
| Treatment A - Platinum Eligible Subgroup Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy.
Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W | 123 |
| Treatment B - Platinum Eligible Subgroup Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy.
Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W | 61 |
| Total | 425 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Randomization | AE unrelated to Study Drug | 1 | 0 | 0 | 0 |
| Randomization | Disease Progression | 0 | 0 | 1 | 0 |
| Treatment Period | Adverse Event unrelated to to study Drug | 10 | 2 | 9 | 2 |
| Treatment Period | Death | 0 | 0 | 3 | 1 |
| Treatment Period | Disease Progression | 113 | 64 | 82 | 43 |
| Treatment Period | Lost to Follow-up | 1 | 1 | 0 | 0 |
| Treatment Period | Maximum Clinical Benefit | 8 | 4 | 7 | 1 |
| Treatment Period | Other reasons | 5 | 9 | 3 | 6 |
| Treatment Period | Participant no longer meets study criteria | 0 | 0 | 1 | 0 |
| Treatment Period | Participant request to discontinue | 5 | 0 | 3 | 2 |
| Treatment Period | Participant withdrew consent | 4 | 0 | 0 | 1 |
| Treatment Period | Poor/Non Compliance | 1 | 0 | 0 | 1 |
| Treatment Period | Study Drug Toxicity | 11 | 2 | 14 | 4 |
Baseline characteristics
| Characteristic | Treatment A - Platinum Refractory Subgroup | Treatment B - Platinum Refractory Subgroup | Treatment A - Platinum Eligible Subgroup | Treatment B - Platinum Eligible Subgroup | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 40 Participants | 19 Participants | 44 Participants | 21 Participants | 124 Participants |
| Age, Categorical Between 18 and 65 years | 119 Participants | 63 Participants | 79 Participants | 40 Participants | 301 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 7 Participants | 6 Participants | 6 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 23 Participants | 66 Participants | 25 Participants | 170 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 93 Participants | 52 Participants | 51 Participants | 30 Participants | 226 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 3 Participants | 1 Participants | 1 Participants | 18 Participants |
| Race (NIH/OMB) White | 141 Participants | 75 Participants | 120 Participants | 58 Participants | 394 Participants |
| Sex: Female, Male Female | 29 Participants | 18 Participants | 18 Participants | 14 Participants | 79 Participants |
| Sex: Female, Male Male | 130 Participants | 64 Participants | 105 Participants | 47 Participants | 346 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 131 / 159 | 71 / 82 | 102 / 123 | 49 / 61 |
| other Total, other adverse events | 139 / 158 | 76 / 82 | 118 / 122 | 54 / 61 |
| serious Total, serious adverse events | 103 / 158 | 52 / 82 | 89 / 122 | 35 / 61 |
Outcome results
Primary
Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup
The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.
Time frame: Approximately up to 30 months (from FPFV to Data base lock)
Population: Platinum Refractory Responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | NA Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | 11.07 Months |
Primary
Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup
ORR is defined as best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Approximately up to 30 months (from FPFV to Data base lock)
Population: All Randomized Participants - Platinum Refractory Subgroup
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | 13.2 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | 18.3 percentage of participants |
Comparison: Treatment A over Treatment Bp-value: 0.289795.5% CI: [0.33, 1.43]Mantel Haenszel
Primary
Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup
Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Approximately up to 30 months (from FPFV to Data base lock)
Population: Platinum refractory responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | 2.56 Months |
| Treatment B - Platinum Refractory Subgroup | Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | 1.51 Months |
Secondary
Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup
The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum eligible subgroup responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup | 27.04 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup | 24.61 Months |
Secondary
Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status
The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: All treated participants in the Platinum Eligible subgroup with a response
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status | Negative | 27.04 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status | Positive | 33.84 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status | Negative | 19.32 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status | Positive | 48.49 Months |
Secondary
Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status
The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum Eligible Responders
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 33.84 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: > 50% | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 13.13 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: < 25% | 13.17 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: Unquantifiable | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: <50% | 13.67 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: Unquantifiable | 28.99 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: < 25% | 12.42 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | NA Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: <50% | 15.87 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: > 50% | NA Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 6.21 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 24.61 Months |
Secondary
Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status
The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: All treated participants in the Platinum eligible subgroup with a response
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 10 | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <10 | 13.67 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: Not Reported | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <7 | 10.97 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB ≥ 7 | 24.11 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <10 | NA Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <7 | NA Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 10 | 19.32 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB ≥ 7 | 19.32 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: Not Reported | 48.49 Months |
Secondary
Duration of Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status
The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: All treated participants in the Platinum Refractory subgroup with a response
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status | HPV p-16 Positive | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status | HPV p-16 Negative | 39.43 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status | HPV p-16 Positive | 11.10 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status | HPV p-16 Negative | 8.34 Months |
Secondary
Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status
The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: All treated participants in the Platinum refractory subgroup with a response
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: Unquantifiable | 38.67 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: > 50% | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 39.43 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: < 25% | 39.43 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: <50% | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 39.43 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: < 25% | 11.10 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: > 50% | 6.24 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | NA Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: <50% | 11.14 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 8.34 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | 8.34 Months |
Secondary
Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status
The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: All treated participants in the Platinum Refractory subgroup with a response
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <7 | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB ≥ 7 | 38.67 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <10 | NA Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: Not Reported | 26.71 Months |
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 10 | 38.67 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 10 | 7.54 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <7 | 11.14 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <10 | 11.14 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB ≥ 7 | 8.59 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: Not Reported | 8.21 Months |
Secondary
Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup
ORR is defined as percentage of participants with a complete response (CR) or partial response (PR). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to end of study. Approximately 63 Months
Population: All Randomized Participants - Platinum Eligible Subgroup
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup | 20.3 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup | 29.5 percentage of participants |
Secondary
ORR - Platinum Eligible Subgroup Based on HPV p-16 Status
ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to end of study. Approximately 63 Months
Population: All Randomized Participants - Platinum Eligible Subgroup
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on HPV p-16 Status | Positive | 20.0 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on HPV p-16 Status | Negative | 20.5 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on HPV p-16 Status | Positive | 41.2 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on HPV p-16 Status | Negative | 25.0 percentage of participants |
Secondary
ORR - Platinum Eligible Subgroup Based on PD-L1 Expression
ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to end of study. Approximately 63 Months
Population: Platinum Eligible Subgroup
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: ≥ 25% | 31.0 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: <50% | 16.7 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | <1% | 15.7 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: ≥ 1% | 21.5 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: < 25% | 14.9 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: > 50% | 30.0 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: 1 - < 25% | 13.9 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | Without quantifiable PD-L1 expression at baseline | NA percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: ≥ 1% | 30.3 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: ≥ 25% | 31.6 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: > 50% | 33.3 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: <50% | 24.4 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | Without quantifiable PD-L1 expression at baseline | NA percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: < 25% | 24.3 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | <1% | 21.7 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on PD-L1 Expression | PD-L1: 1 - < 25% | 28.6 percentage of participants |
Secondary
ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker
ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to end of study. Approximately 63 Months
Population: All Randomized Participants - Platinum Eligible Subgroup
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB < 10 | 17.3 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB < 7 | 10.2 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB ≥ 7 | 34.2 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB ≥ 10 | 31.3 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB Not Reported | 23.1 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB ≥ 10 | 33.3 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB ≥ 7 | 28.6 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB Not Reported | 28.6 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB < 10 | 28.6 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB < 7 | 30.8 percentage of participants |
Secondary
ORR - Platinum Refractory Subgroup Based on HPV p-16 Status
ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to end of study. Approximately 63 Months
Population: All Randomized Participants - Platinum Refractory Subgroup
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on HPV p-16 Status | OROPHARYNGEAL HPV P-16 POSITIVE | 23.3 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on HPV p-16 Status | OROPHARYNGEAL HPV P-16 NEGATIVE/ NON-OROPHARYNGEAL | 12.4 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on HPV p-16 Status | OROPHARYNGEAL HPV P-16 POSITIVE | 37.5 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on HPV p-16 Status | OROPHARYNGEAL HPV P-16 NEGATIVE/ NON-OROPHARYNGEAL | 16.7 percentage of participants |
Secondary
ORR - Platinum Refractory Subgroup Based on PD-L1 Expression
ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to end of study. Approximately 63 Months
Population: Platinum Refractory subgroup
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | <1% | 7.7 Percentage of Participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: ≥ 1% | 19.6 Percentage of Participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: ≥ 25% | 33.3 Percentage of Participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: > 50% | 33.3 Percentage of Participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: < 25% | 11.1 Percentage of Participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: <50% | 13.2 Percentage of Participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: 1 - < 25% | 13.8 Percentage of Participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | without quantifiable PD-L1 expression at baseline | NA Percentage of Participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: < 25% | 21.1 Percentage of Participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | <1% | 25.8 Percentage of Participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: ≥ 25% | 25.0 Percentage of Participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: 1 - < 25% | 15.4 Percentage of Participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: <50% | 22.7 Percentage of Participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | without quantifiable PD-L1 expression at baseline | NA Percentage of Participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: ≥ 1% | 19.6 Percentage of Participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on PD-L1 Expression | PD-L1: > 50% | 18.2 Percentage of Participants |
Secondary
ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker
ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to end of study. Approximately 63 Months
Population: All Randomized Participants - Platinum Refractory Subgroup
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB ≥ 7 | 23.3 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB ≥ 10 | 31.6 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB < 10 | 11.0 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB Not Reported | 14.3 percentage of participants |
| Treatment A - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB < 7 | 9.0 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB Not Reported | 18.2 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB < 7 | 20.5 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB ≥ 7 | 19.0 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB < 10 | 22.4 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker | TMB ≥ 10 | 18.2 percentage of participants |
Secondary
Overall Survival (OS)
Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time frame: From randomization to death. Approximately 63 Months
Population: All Randomized Participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) | 9.76 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) | 11.30 Months |
95% CI: [0.87, 1.36]
Secondary
Overall Survival (OS) - Platinum Eligible Subgroup
Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time frame: From randomization to death. Approximately 63 Months
Population: All Randomized Participants - Platinum Eligible Subgroup
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup | 9.71 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup | 12.91 Months |
95% CI: [0.81, 1.61]
Secondary
Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status
Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time frame: From randomization to death. Approximately 63 Months
Population: All Randomized Participants - Platinum Eligible Subgroup
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status | Positive | 16.66 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status | Negative | 7.79 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status | Negative | 9.46 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status | Positive | 33.74 Months |
Secondary
Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status
Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time frame: From randomization to death. Approximately 63 Months
Population: Platinum Eligible Subgroup
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | <1% | 12.52 months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: < 25% | 8.72 months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 7.56 months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | 12.39 months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: <50% | 9.10 months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: > 50% | 9.40 months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 6.16 months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | Without quantifiable PD-L1 expression at baseline | 26.12 months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | Without quantifiable PD-L1 expression at baseline | 33.74 months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | <1% | 11.17 months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: <50% | 9.92 months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: < 25% | 11.17 months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 8.48 months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 14.00 months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: > 50% | 15.01 months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | 14.00 months |
Secondary
Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status
Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time frame: From randomization to death. Approximately 63 Months
Population: All Randomized Participants - Platinum Eligible Subgroup
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <7 | 7.56 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 7 | 16.30 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 10 | 9.99 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | Not Reported | 8.00 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥10 | 16.72 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥10 | 14.77 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <7 | 18.27 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | Not Reported | 9.71 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 7 | 13.08 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 10 | 15.01 Months |
Secondary
Overall Survival (OS) - Platinum Refractory Subgroup
Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time frame: From randomization to death. Approximately 63 Months
Population: All Randomized Participants - Platinum Refractory Subgroup
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup | 9.76 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup | 9.59 Months |
95% CI: [0.81, 1.45]
Secondary
Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status
Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time frame: From randomization to death. Approximately 63 Months
Population: All Randomized Participants - Platinum Refractory Subgroup
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status | Positive | 13.93 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status | Negative | 9.36 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status | Positive | 14.32 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status | Negative | 9.59 Months |
Secondary
Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status
Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time frame: From randomization to death. Approximately 63 Months
Population: Platinum refractory subgroup
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | Without quantifiable PD-L1 expression at baseline | 6.93 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 10.22 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: <50% | 9.76 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | 5.78 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: > 50% | 26.02 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | <1% | 9.53 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 10.32 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: < 25% | 9.95 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 7.56 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: < 25% | 8.77 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | Without quantifiable PD-L1 expression at baseline | 28.09 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | 10.23 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 9.02 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | <1% | 12.29 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: <50% | 10.61 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: > 50% | 7.33 Months |
Secondary
Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status
Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time frame: From randomization to death. Approximately 63 Months
Population: All Randomized Participants - Platinum Refractory Subgroup
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 10 | 7.52 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥10 | 6.51 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 7 | 11.37 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | Not Reported | 13.86 Months |
| Treatment A - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <7 | 5.78 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | Not Reported | 20.01 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: <7 | 8.77 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 7 | 7.16 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥10 | 9.26 Months |
| Treatment B - Platinum Refractory Subgroup | Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 10 | 8.31 Months |
Secondary
Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup
the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum Eligible subgroup all randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup | 2.76 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup | 2.86 Months |
95% CI: [0.78, 1.41]
Secondary
Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup
The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum Refractory subgroup all randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | 2.50 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup | 2.60 Months |
95% CI: [0.78, 1.41]
Secondary
Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status
the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum eligible subgroup
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status | Postive | 2.92 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status | Negative | 2.66 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status | Postive | 6.83 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status | Negative | 2.83 Months |
Secondary
Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status
The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum eligible subgroup
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | <1% | 2.61 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: <50% | 2.55 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: < 25% | 2.37 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: > 50% | 4.21 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 2.89 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 1.51 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | Without quantifiable PD-L1 expression at baseline | 6.47 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | 5.75 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | Without quantifiable PD-L1 expression at baseline | 13.73 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | <1% | 2.73 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 2.99 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: < 25% | 2.76 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | 2.99 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: <50% | 2.76 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: > 50% | 2.99 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 3.10 Months |
Secondary
Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status
the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum eligible subgroup all randomized
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 7 | 5.82 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 10 | 2.63 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: Not Reported | 2.71 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 10 | 6.97 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 7 | 2.63 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 10 | 2.76 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 7 | 2.92 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 7 | 2.83 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: Not Reported | 3.10 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 10 | 2.99 Months |
Secondary
Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status
the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum Refractory subgroup all randomized
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status | Postive | 4.11 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status | Negative | 1.84 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status | Postive | 6.70 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status | Negative | 1.94 Months |
Secondary
Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status
The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum Refractory subgroup
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | 2.12 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: <50% | 2.60 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 2.60 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: > 50% | 2.79 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: < 25% | 2.60 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 2.66 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | Without Quantifiable PD-L1 expression at Baseline | 2.17 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | <1% | 2.60 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | Without Quantifiable PD-L1 expression at Baseline | 1.71 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 1% | 2.60 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: < 25% | 2.79 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: ≥ 25% | 1.54 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: <50% | 2.79 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: > 50% | 1.54 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | PD-L1: 1 - < 25% | 2.60 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status | <1% | 2.96 Months |
Secondary
Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status
the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum Refractory subgroup all randomized
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 10 | 2.81 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 10 | 1.68 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: Not Reported | 2.66 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 7 | 2.76 Months |
| Treatment A - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 7 | 1.45 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 7 | 2.50 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 7 | 1.54 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: Not Reported | 2.92 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: < 10 | 2.50 Months |
| Treatment B - Platinum Refractory Subgroup | Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status | TMB: ≥ 10 | 1.41 Months |
Post Hoc
Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup - Post Hoc Analysis
The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: From randomization to disease progression or death. Approximately 63 Months
Population: Platinum Refractory Responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup - Post Hoc Analysis | 39.43 Months |
| Treatment B - Platinum Refractory Subgroup | Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup - Post Hoc Analysis | 11.07 Months |
Post Hoc
Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup - Post Hoc Analysis
ORR is defined as best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to end of study. Approximately 63 Months
Population: All Randomized Participants - Platinum Refractory Subgroup
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup - Post Hoc Analysis | 14.5 percentage of participants |
| Treatment B - Platinum Refractory Subgroup | Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup - Post Hoc Analysis | 20.7 percentage of participants |
Comparison: Treatment A over Treatment B95% CI: [0.32, 1.29]Mantel Haenszel
Post Hoc
Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup - Post Hoc Analysis
Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization to a confirmed response. Approximately 35 Months
Population: Platinum refractory responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A - Platinum Refractory Subgroup | Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup - Post Hoc Analysis | 2.63 Months |
| Treatment B - Platinum Refractory Subgroup | Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup - Post Hoc Analysis | 1.71 Months |