An Exploratory Study of the Effects of Nivolumab Combined With Ipilimumab in Patients With Treatment-Naive Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC)

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm. Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum. CR+PR, confidence interval based on the Clopper and Pearson method.

Time frame: From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)

Population: All treated PD-L1 and bTMB evaluable Part 1 and Part 2 participants (Blood TMB Cut-point = 21-mutations/MB). Non-evaluable PD-L1 status means that PD-L1 status could not be determined, thus the Arm population did not meet this criteria. Participants in Part 2: PD-L1(+/-) Status groups were stratified from the PART 2: PD-L1 Status Independent Arm. Not all participants were bTMB evaluable. To be analyzed participants had to be both PD-L1 evaluable and bTMB evaluable.

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm. Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum. CR+PR, confidence interval based on the Clopper and Pearson method.

Time frame: From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)

Population: All treated PD-L1 and bTMB evaluable Part 1 and 2 participants (Blood TMB Cut-point = 16 mutations/MB). Non-evaluable PD-L1 status means that PD-L1 status could not be determined, thus the Arm population did not meet this criteria. Participants in Part 2: PD-L1(+/-) Status groups were stratified from the PART 2: PD-L1 Status Independent Arm. Not all participants were bTMB evaluable. To be analyzed participants had to be both PD-L1 evaluable and bTMB evaluable.

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm. Tissue tumor mutational burden (tTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in tumor tissue samples. CR+PR, confidence interval based on the Clopper and Pearson method.

Time frame: From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 58 months)

Population: All treated PD-L1 and bTMB evaluable Part 1 and Part 2 participants (Blood TMB Cut-point = 10-mutations/MB). Non-evaluable PD-L1 status means that PD-L1 status could not be determined, thus the Arm population did not meet this criteria. Participants in Part 2: PD-L1(+/-) Status groups were stratified from the PART 2: PD-L1 Status Independent Arm. Not all participants were bTMB evaluable. To be analyzed participants had to be both PD-L1 evaluable and bTMB evaluable.

Disease control rate (DCR) is the percent of treated participants with a best overall response of a complete response (CR), partial response (PR), or stable disease (SD), assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in short axis to \<10 mm of any pathological lymph nodes (target or non-target). SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking smallest sum diameters as reference. PD is at least a 20% increase in the sum of diameters of target lesions, taking the smallest sum as reference. The sum must also demonstrate an absolute increase of at least 5 mm. (one or more new lesions is also considered progression). CR+PR, confidence interval based on the Clopper and Pearson method.

Time frame: From first dose until the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy, whichever occurs first (Up to approximately 67 months)

Population: All treated participants in Part 1. Endpoint pre-specified only for participants treated in Part 1.

DOR is the time between first confirmed response (Complete/Partial Response) and first documented tumor progression (per RECIST 1.1) or death due to any cause. Participants who don't progress or die are censored on the date of their last evaluable tumor assessment. Participants who started subsequent anti-cancer therapy without prior reported progression were censored at the last evaluable tumor assessment prior to or on the date of subsequent anti-cancer therapy. PR is at least 30% decrease in the sum of diameters of target lesions, using baseline sum diameters as reference. CR is disappearance of all target lesions and reduction in short axis to \<10 mm of any pathological lymph nodes (target or non-target). Progressive Disease (PD) is at least 20% increase in the sum of diameters of target lesions, taking the smallest sum as reference. The sum must also show an overall increase of \> 5 mm. (one or more new lesions is also progression). Median computed using Kaplan-Meier method.

Time frame: From first dose to the date of the first documented tumor progression or death due to any cause (Up to approximately 67 months)

Population: All treated participants in Part 1 who had complete or partial response. Endpoint pre-specified only for participants treated in Part 1.

An Adverse Event (AE) is any new untoward medical occurrence or worsening preexisting medical condition in a treated participant and that does not necessarily have a causal relationship with treatment. An AE can be any unfavorable, unintended sign, symptom, or disease temporally associated with the use of treatment, whether or not related to the treatment.

Time frame: From first dose to 30 days after last dosing date (assessed up to approximately 27 months)

Population: All treated Part 2 participants. Endpoint pre-specified only for participants treated in Part 2.

An Adverse Event (AE) is any new untoward medical occurrence or worsening preexisting medical condition in a treated participant and that does not necessarily have a causal relationship with treatment. An AE can be any unfavorable, unintended sign, symptom, or disease temporally associated with the use of treatment, whether or not related to the treatment.

Time frame: From first dose to 30 days after last dosing date (up to approximately 27 months)

Population: All treated Part 2 participants. Endpoint pre-specified only for participants treated in Part 2.

A Serious Adverse Event (SAE) results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), or requires inpatient hospitalization or causes prolongation of existing hospitalization.

Time frame: From first dose to 30 days after last dosing date (assessed up to approximately 27 months)

Population: All treated Part 2 participants. Endpoint pre-specified only for participants treated in Part 2.

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response (CR) is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm. CR+PR, confidence interval based on the Clopper and Pearson method.

Time frame: From first dose until the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy, whichever occurs first (Up to approximately 67 months)

Population: All treated Part 1 and Part 2 participants

OS is defined as the time from first dosing date to the date of death. If a participant didn't die, OS will be censored on the last date the participant was known to be alive. Median based on Kaplan-Meier estimates.

Time frame: From first dose to the date of death (Assessed up to approximately 67 months)

Population: All treated Part 1 and Part 2 participants

PFS is defined as the time from first dosing date to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to or on the date of initiation of subsequent anti-cancer therapy. Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking the smallest sum on study as reference. The sum must also show an overall increase of \> 5 mm. (one or more new lesions is also progression). Median calculated using Kaplan-Meier estimates.

Time frame: From first dose to the date of the first documented tumor progression or death due to any causes (Assessed up to approximately 67 months)

Population: All treated Part 1 and Part 2 participants

TTR is the time taken from first dosing date to the time the criteria for Complete Response (CR)/Partial Response (PR) are first met. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

Time frame: From first dose to the time the criteria for Complete Response/Partial Response are first met (Up to approximately 67 months)

Population: All treated participants in Part 1 who had complete or partial response. Endpoint pre-specified only for participants treated in Part 1.

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm. Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum. CR+PR, confidence interval based on the Clopper and Pearson method.

Time frame: From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 67 months)

Population: All treated PD-L1 and bTMB evaluable Part 1 and Part 2 participants (Blood TMB Cut-point = 21-mutations/MB). Non-evaluable PD-L1 status means that PD-L1 status could not be determined, thus the Arm population did not meet this criteria. Not all participants were bTMB evaluable. To be analyzed participants had to be both PD-L1 evaluable and bTMB evaluable.

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm. Blood tumor mutational burden (bTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in serum. CR+PR, confidence interval based on the Clopper and Pearson method.

Time frame: From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 67 months)

Population: All treated PD-L1 and bTMB evaluable Part 1 and 2 participants (Blood TMB Cut-point = 16 mutations/MB). Non-evaluable PD-L1 status means that PD-L1 status could not be determined, thus the Arm population did not meet this criteria. Not all participants were bTMB evaluable. To be analyzed participants had to be both PD-L1 evaluable and bTMB evaluable.

Objective response rate (ORR) is defined as the percent of treated participants with a best overall response of a complete response (CR) or partial response (PR) assessed by investigator per Response Evaluation Criteria In Solid Tumors (RECIST 1.1). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR is disappearance of all target lesions and a reduction in pathological lymph node (whether target or non-target) short axis to \<10 mm. Tissue tumor mutational burden (tTMB) is the total number of nonsynonymous somatic mutations produced by a tumor that are detected in tumor tissue samples. CR+PR, confidence interval based on the Clopper and Pearson method.

Time frame: From first dose up to the date of objectively documented progression, or the date of initiation of palliative local therapy or the date of initiation of subsequent anticancer therapy (up to approximately 67 months)

Population: All treated PD-L1 and bTMB evaluable Part 1 and Part 2 participants (Blood TMB Cut-point = 10-mutations/MB). Non-evaluable PD-L1 status means that PD-L1 status could not be determined, thus the Arm population did not meet this criteria. Not all participants were bTMB evaluable. To be analyzed participants had to be both PD-L1 evaluable and bTMB evaluable.