NCT03215706 · CITED IN SOURCE DOCUMENTS

A Study of Nivolumab and Ipilimumab Combined With Chemotherapy Compared to Chemotherapy Alone in First Line NSCLC

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2025-12-17

The purpose of this study is to determine whether Nivolumab, Ipilimumab combined with chemotherapy is more effective than chemotherapy by itself when treating stage IV NSCLC as the first treatment given for the disease

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Progression Free Survival (PFS) by BICR

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outcome · POSTED

Objective Response Rate (ORR) by BICR

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outcome · POSTED

Duration of Response (DoR)

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outcome · POSTED

Time to Response (TTR)

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outcome · POSTED

Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression

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outcome · POSTED

PFS by BICR by PD-L1 Tumor Cell Expression

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outcome · POSTED

OS by PD-L1 Tumor Cell Expression

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

PFS by BICR by Tumor Mutational Burden

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outcome · POSTED

ORR by BICR by Tumor Mutational Burden

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outcome · POSTED

OS by Tumor Mutational Burden

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Participants with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy * Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 * Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria * Participants must have PD-L1 IHC testing with results performed by a central laboratory during the screening period Exclusion Criteria: * Participants with known epidermal growth factor receptor (EGFR) mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 \[L858R\] substitution mutations) are excluded * Participants with known anaplastic lymphoma kinase (ALK) translocations which are sensitive to available targeted inhibitor therapy are excluded * Participants with untreated CNS metastases are excluded. Participants are eligible if CNS metastases are adequately treated and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment Other protocol inclusion/exclusion criteria may apply
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Chemotherapy/Biologics combined
intervention Names
Biological: Ipilimumab
Biological: Nivolumab
Drug: Carboplatin
Drug: Paclitaxel
Drug: Pemetrexed
Drug: Cisplatin
label
Module A
type
EXPERIMENTAL
description
Chemotherapy Combination
intervention Names
Drug: Carboplatin
Drug: Paclitaxel
Drug: Pemetrexed
Drug: Cisplatin
label
Module B
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Module A
description
Specified dose on specified day
name
Ipilimumab
other Names
Yervoy, BMS734016
type
BIOLOGICAL
arm Group Labels
Module A
description
Specified dose on specified day
name
Nivolumab
other Names
Opdivo, BMS936558
type
BIOLOGICAL
arm Group Labels
Module A
Module B
description
Specified dose on specified day
name
Carboplatin
type
DRUG
arm Group Labels
Module A
Module B
description
Specified dose on specified day
name
Paclitaxel
other Names
Taxol
type
DRUG
arm Group Labels
Module A
Module B
description
Specified dose on specified day
name
Pemetrexed
other Names
Alimta
type
DRUG
arm Group Labels
Module A
Module B
description
Specified dose on specified day
name
Cisplatin
other Names
Platinol
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 719
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
measure
Overall Survival (OS)
time Frame
From date of randomization to date of death (assessed up to October 2019, approximately 23 months)

secondary Outcomes

description
PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
measure
Progression Free Survival (PFS) by BICR
time Frame
From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
description
ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression.
measure
Objective Response Rate (ORR) by BICR
time Frame
From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
description
DoR was defined as the time between the date of first confirmed documented response (CR or PR) to the date of the first documented BICR-assessed tumor progression (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who started subsequent therapy (including palliative local therapy) without a prior reported progression were censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy (including palliative local therapy). Participants who died without a reported prior progression were considered to have progressed on the date of their death. For subjects who neither progressed nor died, DoR was censored on the date of their last evaluable tumor assessment. DoR was evaluated for responders (confirmed CR or PR) only.
measure
Duration of Response (DoR)
time Frame
From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
description
TTR was defined as the time from randomization to the date of the first confirmed documented response (CR or PR), as assessed by the BICR. TTR was evaluated for responders (confirmed CR or PR) only.
measure
Time to Response (TTR)
time Frame
From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
description
ORR was defined as the proportion of randomized participants with a best overall response (BOR) of confirmed complete or partial response per BICR using RECIST v1.1. BOR was assessed from randomization until documented progression, start of palliative local or subsequent anti-cancer therapy-whichever came first. If none occurred, all response data contributed to BOR. For those treated beyond progression, BOR was based on responses before initial RECIST-defined progression. PD-L1 expression was measured via Dako PD-L1 IHC 28-8 pharmDx test as the percentage of tumor cells with membrane staining among ≥100 evaluable cells. Expression was categorized as ≥1%, \<1%, not quantifiable, ≥50%, or 1-49%.
measure
Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression
time Frame
From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
description
PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
measure
PFS by BICR by PD-L1 Tumor Cell Expression
time Frame
From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
description
OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
measure
OS by PD-L1 Tumor Cell Expression
time Frame
From date of randomization to date of death (assessed up to October 2024, approximately 72 months)
description
PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first.
measure
PFS by BICR by Tumor Mutational Burden
time Frame
From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
description
ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression.
measure
ORR by BICR by Tumor Mutational Burden
time Frame
From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2024, approximately 72 months)
description
OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date.
measure
OS by Tumor Mutational Burden
time Frame
From date of randomization to date of death (assessed up to October 2024, approximately 72 months)

Full study description

brief Summary: The purpose of this study is to determine whether Nivolumab, Ipilimumab combined with chemotherapy is more effective than chemotherapy by itself when treating stage IV NSCLC as the first treatment given for the disease

Source references

references

citation
Nishio M, Hayashi H, Goto Y, Ikeda S, Yokoyama T, Tanaka H, Tambo Y, Hotta K, Fukuhara T, Daga H, Masubuchi K, Aoyama T, Tschaika M, Hu N, Mizutani H. Nivolumab plus ipilimumab-based treatment in Japanese patients with metastatic non-small cell lung cancer and tumor PD-L1 < 1%: a pooled analysis. Int J Clin Oncol. 2026 Aug 11. doi: 10.1007/s10147-026-03116-w. Online ahead of print.
pmid
42579028
type
DERIVED
citation
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pmid
39369790
type
DERIVED
citation
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pmid
39270380
type
DERIVED
citation
Paz-Ares L, Ciuleanu TE, Cobo M, Schenker M, Zurawski B, Menezes J, Richardet E, Bennouna J, Felip E, Juan-Vidal O, Alexandru A, Sakai H, Lingua A, Salman P, Souquet PJ, De Marchi P, Martin C, Perol M, Scherpereel A, Lu S, John T, Carbone DP, Meadows-Shropshire S, Agrawal S, Oukessou A, Yan J, Reck M. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):198-211. doi: 10.1016/S1470-2045(20)30641-0. Epub 2021 Jan 18.
pmid
33476593
type
DERIVED