A Study of Nivolumab and Ipilimumab Combined With Chemotherapy Compared to Chemotherapy Alone in First Line NSCLC (CheckMate 9LA)

• ClinicalTrials.gov Identifier: NCT03215706
• Recruitment Status: Active, not recruiting
• First Posted: July 12, 2017
• Results First Posted: September 16, 2020
• Last Update Posted: January 10, 2024
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: July 11, 2017
• First Posted Date: July 12, 2017
• Results First Submitted Date: August 15, 2020
• Results First Posted Date: September 16, 2020
• Last Update Posted Date: January 10, 2024
• Actual Study Start Date: August 24, 2017
• Actual Primary Completion Date: August 16, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 15, 2020)

Overall Survival (OS) [ Time Frame: From date of randomization to date of death (assessed up to October 2019, approximately 23 months) ]

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.

Original Primary Outcome Measures (submitted: July 11, 2017)

Overall Survival (OS) [ Time Frame: Up to 25 months ]

To compare the efficacy of nivolumab + ipilimumab combined with chemotherapy versus (vs)chemotherapy

Current Secondary Outcome Measures (submitted: August 15, 2020)

• 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 2019, approximately 23 months) ]
  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.
• Objective Response Rate (ORR) by BICR [ Time Frame: From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months) ]
  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.
• Duration of Response (DoR) [ Time Frame: From date of first confirmed response to date of tumor progression (assessed up to October 2019, approximately 23 months) ]
  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.
• Time to Response (TTR) [ Time Frame: From date of randomization to date of first confirmed documented response (assessed up to October 2019, approximately 23 months) ]
  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.
• 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 subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months) ]
  PD-L1 expression was defined as the percent of tumor cells with membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC 28-8 pharmDx test. PD-L1 expression was classified as PD-L1 ≥1% (≥1% tumor cells with membrane staining in a minimum of a hundred evaluable tumor cells), PD-L1 < 1% and PD-L1 not quantifiable (without quantifiable PD-L1 expression), PD-L1 expression ≥ 50%, PD-L1 expression 1 to 49%
• 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 2019, approximately 23 months) ]
  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.
• OS by PD-L1 Tumor Cell Expression [ Time Frame: From date of randomization to date of death (assessed up to October 2019, approximately 23 months) ]
  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.

Original Secondary Outcome Measures (submitted: July 11, 2017)

• Progression Free Survival (PFS) [ Time Frame: Up to 25 months ]
  To compare the efficacy of nivolumab + ipilimumab combined with chemotherapy vs chemotherapy
• Overall Response Rate (ORR) [ Time Frame: Up to 25 months ]
  To compare the efficacy of nivolumab + ipilimumab combined with chemotherapy vs chemotherapy
• ORR [ Time Frame: Up to 25 months ]
  In participants with different PD-L1 levels
• PFS [ Time Frame: Up to 25 months ]
  In participants with different PD-L1 levels
• OS [ Time Frame: Up to 25 months ]
  In participants with different PD-L1 levels
• ORR [ Time Frame: Up to 25 months ]
  In association with tumor cell total somatic mutation numbers
• PFS [ Time Frame: Up to 25 months ]
  In association with tumor cell total somatic mutation numbers
• OS [ Time Frame: Up to 25 months ]
  In association with tumor cell total somatic mutation numbers

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Nivolumab and Ipilimumab Combined With Chemotherapy Compared to Chemotherapy Alone in First Line NSCLC
• Official Title: A Phase 3, Randomized Study of Nivolumab Plus Ipilimumab in Combination With Chemotherapy vs Chemotherapy Alone as First Line Therapy in Stage IV Non-Small Cell Lung Cancer
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Biological: Ipilimumab
  Specified dose on specified day
  Other Name: Yervoy, BMS734016
• Biological: Nivolumab
  Specified dose on specified day
  Other Name: Opdivo, BMS936558
• Drug: Carboplatin
  Specified dose on specified day
• Drug: Paclitaxel
  Specified dose on specified day
  Other Name: Taxol
• Drug: Pemetrexed
  Specified dose on specified day
  Other Name: Alimta
• Drug: Cisplatin
  Specified dose on specified day
  Other Name: Platinol

Study Arms

• Experimental: Module A
  Chemotherapy/Biologics combined
  Interventions:

  • Biological: Ipilimumab
  • Biological: Nivolumab
  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Pemetrexed
  • Drug: Cisplatin
• Active Comparator: Module B
  Chemotherapy Combination
  Interventions:

  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Drug: Pemetrexed
  • Drug: Cisplatin

• Publications *: 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. Erratum In: Lancet Oncol. 2021 Mar;22(3):e92.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 15, 2020): 719
• Original Estimated Enrollment (submitted: July 11, 2017): 420
• Estimated Study Completion Date: January 19, 2026
• Actual Primary Completion Date: August 16, 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, Chile, China, France, Germany, Ireland, Italy, Japan, Mexico, Poland, Romania, Russian Federation, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03215706
• Other Study ID Numbers: CA209-9LA; 2017-001195-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: January 2024