A Neoadjuvant Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Versus Chemotherapy Alone in Early Stage Non-Small Cell Lung Cancer (NSCLC) (CheckMate 816)

• ClinicalTrials.gov Identifier: NCT02998528
• Recruitment Status: Active, not recruiting
• First Posted: December 20, 2016
• Results First Posted: September 28, 2022
• Last Update Posted: October 16, 2023
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: December 16, 2016
• First Posted Date: December 20, 2016
• Results First Submitted Date: August 31, 2022
• Results First Posted Date: September 28, 2022
• Last Update Posted Date: October 16, 2023
• Actual Study Start Date: March 4, 2017
• Actual Primary Completion Date: September 8, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 31, 2022)

• Event-Free Survival (EFS) [ Time Frame: From randomization to disease progression, reoccurrence, or death due to any cause. (Up to a median of 30 months) ]
  Event-free survival (EFS) is defined as the length of time from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on blinded independent central review (BICR) assessment per response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum 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).
• Pathologic Complete Response (pCR) Rate [ Time Frame: From randomization up to a median of 30 months after randomization. ]
  Pathologic complete response (pCR) rate is defined as the number of randomized participants with absence of residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review (BIPR).

• Original Primary Outcome Measures (submitted: December 16, 2016): Major Pathological Response (MPR) rate [ Time Frame: At time of surgery ]

Current Secondary Outcome Measures (submitted: August 31, 2022)

• Major Pathologic Response (MPR) Rate [ Time Frame: From randomization up to a median of 30 months after randomization. ]
  Major pathologic response (MPR) rate is defined as number of randomized participants with </= 10% residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review (BIPR). Viable tumors in situ carcinoma should not be included in MPR calculation.
• Overall Survival (OS) [ Time Frame: From randomization to the date of death ]
  Overall survival (OS) is defined as the time between the date of randomization and the date of death. OS will be censored on the last date a participant was known to be alive.
• Time to Death or Distant Metastases (TTDM) [ Time Frame: From randomization to the first date of distant metastasis or the date of death in the absence of distant metastasis (Up to a median of 30 months) ]
  TTDM is defined as the time between the date of randomization and the first date of distant metastasis or the date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the thorax using blinded independent central review (BICR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Patients who have not developed distant metastasis or died at the time of analysis will be censored on the date of their last evaluable tumor assessment.

Original Secondary Outcome Measures (submitted: December 16, 2016)

• Event free survival (EFS) [ Time Frame: Up to approximately 130 months ]
• Overall survival (OS) [ Time Frame: Up to approximately 130 months ]
• Complete pathological response (pCR) [ Time Frame: At time of surgery ]

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

Descriptive Information

• Brief Title: A Neoadjuvant Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Versus Chemotherapy Alone in Early Stage Non-Small Cell Lung Cancer (NSCLC)
• Official Title: Randomized, OpenLabel, Phase 3 Trial of Nivolumab Plus Ipilimumab or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Early Stage NSCLC

Brief Summary

The purpose of this neoadjuvant study is to compare nivolumab plus chemotherapy and chemotherapy alone in terms of safety and effectiveness, and to describe nivolumab plus ipilimumab's safety and effectiveness in treating resectable NSCLC.

This study has multiple primary endpoints.

• 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: Nivolumab
  Specified dose on specified days
  Other Names:

  • BMS-936558
  • Opdivo
• Drug: Cisplatin
  Specified dose on specified days
• Drug: Vinorelbine
  Specified dose on specified days
• Drug: Gemcitabine
  Specified dose on specified days
• Drug: Docetaxel
  Specified dose on specified days
• Drug: Pemetrexed
  Specified dose on specified days
• Drug: Carboplatin
  Specified dose on specified days
• Drug: Paclitaxel
  Specified dose on specified days
• Biological: Ipilimumab
  This arm is closed and no longer enrolling patients.
  Other Names:

  • BMS-734016
  • Yervoy

Study Arms

• Active Comparator: Platinum doublet chemotherapy
  Specified dose on specified days
  Interventions:

  • Drug: Cisplatin
  • Drug: Vinorelbine
  • Drug: Gemcitabine
  • Drug: Docetaxel
  • Drug: Pemetrexed
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Experimental: Nivolumab plus platinum doublet chemotherapy
  Specified dose on specified days
  Interventions:

  • Biological: Nivolumab
  • Drug: Cisplatin
  • Drug: Gemcitabine
  • Drug: Pemetrexed
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Experimental: Nivolumab plus Ipilimumab
  Specified dose on specified days
  Interventions:

  • Biological: Nivolumab
  • Biological: Ipilimumab

• Publications *: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 28, 2022): 505
• Original Estimated Enrollment (submitted: December 16, 2016): 326
• Estimated Study Completion Date: November 8, 2028
• Actual Primary Completion Date: September 8, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Early stage IB-IIIA, operable non-small cell lung cancer, confirmed in tissue
• Lung function capacity capable of tolerating the proposed lung surgery
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Available tissue of primary lung tumor

Exclusion Criteria:

• Presence of locally advanced, inoperable or metastatic disease
• Participants with active, known or suspected autoimmune disease
• Prior treatment with any drug that targets T cell co-stimulations pathways (such as checkpoint inhibitors)

Other protocol defined inclusion/exclusion criteria 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, Brazil, Canada, China, France, Greece, Hungary, Italy, Japan, Korea, Republic of, Romania, Spain, Taiwan, Turkey, United States
• Removed Location Countries: South Africa

Administrative Information

• NCT Number: NCT02998528
• Other Study ID Numbers: CA209-816; 2016-003536-21 ( 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: Ono Pharmaceutical Co. Ltd

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: October 2023