Trial Outcomes & Findings for Platinum-Based Chemotherapy With/Without INCMGA00012, an Anti-PD-1 Antibody, in Non-Small Cell Lung Cancer (NCT NCT04205812)

NCT ID: NCT04205812

Last Updated: 2025-09-25

Results Overview

Overall survival was defined as the time between the date of randomization and the date of death due to any cause.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

583 participants

Primary outcome timeframe

up to 39.1 months

Results posted on

2025-09-25

Participant Flow

This study was conducted in Bulgaria, Brazil, China, Czech Republic, Georgia, Malaysia, Philippines, Poland, Romania, Russia, Serbia, Turkey, Ukraine, United States, Vietnam, and South Africa. Data collected through 15 December 2023 have been included in this results summary.

Participant milestones

Participant milestones
Measure	Placebo + Chemotherapy Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination. Participants who experienced progressive disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) verified by blinded independent central review (BICR) had the opportunity to receive retifanlimab 375 mg IV Q3W for up to approximately 2 years (or up to 35 cycles \[21-day cycles\]) in the optional monotherapy treatment period.	Retifanlimab + Chemotherapy Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Randomized Treatment Period STARTED	192	391
Randomized Treatment Period COMPLETED	59	0
Randomized Treatment Period NOT COMPLETED	133	391
Monotherapy Treatment Period STARTED	59	0
Monotherapy Treatment Period COMPLETED	0	0
Monotherapy Treatment Period NOT COMPLETED	59	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo + Chemotherapy Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination. Participants who experienced progressive disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) verified by blinded independent central review (BICR) had the opportunity to receive retifanlimab 375 mg IV Q3W for up to approximately 2 years (or up to 35 cycles \[21-day cycles\]) in the optional monotherapy treatment period.	Retifanlimab + Chemotherapy Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Randomized Treatment Period Ongoing	28	138
Randomized Treatment Period Death	94	226
Randomized Treatment Period Lost to Follow-up	5	11
Randomized Treatment Period Physician Decision	1	4
Randomized Treatment Period Withdrawal by Subject	4	11
Randomized Treatment Period Progressive Disease	0	1
Randomized Treatment Period Met Exclusion Criteria	1	0
Monotherapy Treatment Period Ongoing	17	0
Monotherapy Treatment Period Death	39	0
Monotherapy Treatment Period Lost to Follow-up	2	0
Monotherapy Treatment Period Withdrawal by Subject	1	0

Baseline Characteristics

Platinum-Based Chemotherapy With/Without INCMGA00012, an Anti-PD-1 Antibody, in Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo + Chemotherapy n=192 Participants Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination. Participants who experienced progressive disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) verified by blinded independent central review (BICR) had the opportunity to receive retifanlimab 375 mg IV Q3W for up to approximately 2 years (or up to 35 cycles \[21-day cycles\]) in the optional monotherapy treatment period.	Retifanlimab + Chemotherapy n=391 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Total n=583 Participants Total of all reporting groups
Age, Continuous	63.0 years STANDARD_DEVIATION 8.34 • n=5 Participants	62.8 years STANDARD_DEVIATION 8.44 • n=7 Participants	62.8 years STANDARD_DEVIATION 8.40 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	73 Participants n=7 Participants	116 Participants n=5 Participants
Sex: Female, Male Male	149 Participants n=5 Participants	318 Participants n=7 Participants	467 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	15 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	184 Participants n=5 Participants	375 Participants n=7 Participants	559 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	127 Participants n=5 Participants	260 Participants n=7 Participants	387 Participants n=5 Participants
Race/Ethnicity, Customized Black/African-American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black/White biracial	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian	62 Participants n=5 Participants	127 Participants n=7 Participants	189 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 39.1 months

Population: Median survival time in months was estimated using the Kaplan-Meier method. The confidence interval for median survival time was calculated using the method of Brookmeyer and Crowley. Full Analysis Set: all participants to whom study treatment had been assigned by randomization. Participants were analyzed according to the treatment and strata they had been assigned to during the randomization procedure.

Overall survival was defined as the time between the date of randomization and the date of death due to any cause.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=192 Participants Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=391 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Overall Survival	13.4 months Interval 11.0 to 16.7	18.1 months Interval 16.2 to 21.0

SECONDARY outcome

Timeframe: up to 35.8 months

Population: Full Analysis Set. Median PFS time was estimated using the Kaplan-Meier method. The confidence interval for median PFS time was calculated using the method of Brookmeyer and Crowley.

PFS was defined as the length of time from the date of randomization until the earliest date of disease progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as determined by blinded independent central review (BICR), or death due to any cause, if occurring sooner than progression.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=192 Participants Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=391 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Progression-free Survival (PFS)	5.5 months Interval 4.4 to 5.7	7.7 months Interval 6.9 to 9.0

SECONDARY outcome

Timeframe: up to 35.78 months

Population: Full Analysis Set. Confidence intervals were calculated based on the exact method for binomial distributions.

Objective response rate was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 based on BICR at any post-Baseline visit until the first progressive disease or new anticancer therapy. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=192 Participants Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=391 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Objective Response Rate	38.5 percentage of participants Interval 31.6 to 45.8	51.7 percentage of participants Interval 46.6 to 56.7

SECONDARY outcome

Timeframe: up to 34.3 months

Population: Full Analysis Set. Only those participants with a confirmed response were analyzed. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method and Klein and Moeschberger's method with log-log transformation.

Duration of response was defined as the time from the earliest date of documented response until the earliest date of disease progression or death from any cause, whichever comes first, per RECIST v1.1 based on BICR. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=74 Participants Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=202 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Duration of Response	6.1 months Interval 4.2 to 8.3	12.7 months Interval 9.4 to 15.2

SECONDARY outcome

Timeframe: up to approximately 39 months

Population: Safety Population: all participants who received at least 1 dose of study treatment. Treatment groups for this population were determined by the actual treatment that the participant received regardless of treatment assignment at randomization.

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of pre-existing events after the first dose of retifanlimab/placebo and within 90 days of the last administration of the randomized period. AEs that occurred after new anticancer therapy (including monotherapy treatment) were to be excluded.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=190 Participants Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=389 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) in the Randomized Treatment Period	183 Participants	369 Participants

SECONDARY outcome

Timeframe: up to approximately 39 months

Population: Safety Population

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of pre-existing events after the first dose of retifanlimab/placebo and within 90 days of the last administration of the randomized period. AEs that occurred after new anticancer therapy (including monotherapy treatment) were to be excluded.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=190 Participants Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=389 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Number of Participants Who Discontinued Study Drug Due to TEAEs in the Randomized Treatment Period	9 Participants	33 Participants

SECONDARY outcome

Timeframe: up to approximately 27 months

Population: Monotherapy Analysis Set: all participants who were randomized to the placebo group and received at least 1 dose of placebo, who then transitioned and received at least 1 dose of retifanlimab

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=59 Participants Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Number of Participants With Any TEAE in the Monotherapy Treatment Period	50 Participants	—

SECONDARY outcome

Timeframe: up to approximately 27 months

Population: Monotherapy Analysis Set

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy n=59 Participants Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Number of Participants Who Discontinued Study Drug Due to TEAEs in the Monotherapy Treatment Period	4 Participants	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: pre-infusion and immediately after infusion

Population: Pharmacokinetic (PK) Evaluable Population: all participants who received at least 1 dose of retifanlimab and provided at least 1 PK post-dose sample

Cmax1 was defined as the first-dose maximum serum concentration of retifanlimab.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=384 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Cmax1 of Retifanlimab When Administered With Chemotherapy	—	109 milligrams per liter (mg/L) Geometric Coefficient of Variation 23.1

SECONDARY outcome

Timeframe: Cycle 1 Day 1: pre-infusion and immediately after infusion

Population: PK Evaluable Population

AUC1 was defined as the first-dose area under the serum concentration versus time curve.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=384 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
AUC1 of Retifanlimab When Administered With Chemotherapy	—	775 mg/L x day Geometric Coefficient of Variation 25.0

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (C1D1): pre-infusion and immediately after infusion (IAI). C2D1: pre-infusion. C4D1: pre-infusion and IAI. C6D11: pre-infusion. C8D1, and every 4 cycles thereafter: pre-infusion. End of treatment visit and 30-day safety follow-up visit.

Population: PK Evaluable Population

Cmaxss was defined as the maximum serum concentration of retifanlimab at steady state.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=384 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
Cmaxss of Retifanlimab When Administered With Chemotherapy	—	109 mg/L Geometric Coefficient of Variation 23.1

SECONDARY outcome

Population: PK Evaluable Population

AUCss was defined as the area under the serum concentration versus time curve at steady state.

Outcome measures

Outcome measures
Measure	Placebo + Chemotherapy Participants received placebo intravenously (IV) every 3 weeks (Q3W) along with a standard-of-care chemotherapy regimen in the randomized treatment period. Participants with nonsquamous non-small cell lung cancer (NSCLC) received placebo IV (on Day 1 \[D1\]) Q3W with pemetrexed 500 milligrams per meters squared (mg/m\^2) + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by placebo IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received placebo IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by placebo IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.	Retifanlimab + Chemotherapy n=384 Participants Participants received retifanlimab 375 mg IV Q3W along with a standard-of-care platinum-based chemotherapy regimen in the randomized treatment period. Participants with nonsquamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with pemetrexed 500 mg/m\^2 + either cisplatin 75 mg/m\^2 (on D1) Q3W or carboplatin AUC 5 (on D1) Q3W for 4 cycles (21-day cycles) followed by retifanlimab 375 mg IV Q3W + pemetrexed 500 mg/m\^2 Q3W until progression. Participants with squamous NSCLC received retifanlimab 375 mg IV (on D1) Q3W with carboplatin AUC 6 (D1) + either paclitaxel 200 mg/m\^2 (on D1) or nab-paclitaxel 100 mg/m\^2 (on D1, D8, D15) Q3W for 4 cycles followed by retifanlimab 375 mg IV Q3W until progression. Treatment could continue for up to 2 years until unacceptable toxicity, disease progression, investigator's decision, pregnancy, withdrawal of consent, or study termination.
AUCss of Retifanlimab When Administered With Chemotherapy	—	791 mg/L x day Geometric Coefficient of Variation 23.1

Adverse Events

Retifanlimab + Chemotherapy

Serious events: 158 serious events

Other events: 350 other events

Deaths: 234 deaths

Placebo + Chemotherapy

Serious events: 57 serious events

Other events: 177 other events

Deaths: 140 deaths

Randomized Treatment Period Total

Serious events: 215 serious events

Other events: 527 other events

Deaths: 374 deaths

Retifanlimab Monotherapy

Serious events: 12 serious events

Other events: 44 other events

Deaths: 42 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Incyte Corporation

Phone: 1-855-463-3463

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
Publication restrictions are in place

Restriction type: OTHER