A Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Removal and Adjuvant Treatment With Nivolumab or Placebo for Participants With Surgically Removable Early Stage Non-small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT04025879
• Recruitment Status: Active, not recruiting
• First Posted: July 19, 2019
• Last Update Posted: April 8, 2024
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: July 17, 2019
• First Posted Date: July 19, 2019
• Last Update Posted Date: April 8, 2024
• Actual Study Start Date: November 5, 2019
• Actual Primary Completion Date: July 26, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 17, 2019): Event-Free Survival (EFS) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: 5 Years from randomization ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 6, 2020)

• Overall Survival (OS) [ Time Frame: Up to 5 years from randomization ]
• Pathologic Complete Response (pCR) Rate as Assessed by Blinded Independent Pathology Review (BIPR) [ Time Frame: At the time of surgery, between week 12 to week 18 ]
• Major Pathological Response (MPR) Rate as Assessed by Blinded Independent Pathology Review [ Time Frame: Up to 8 weeks following completion of neoadjuvant surgery, approximately study week 22 ]
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: Up to 80 weeks ]
• Incidence of Adverse Events (AEs) [ Time Frame: Up to 80 weeks ]

Original Secondary Outcome Measures (submitted: July 17, 2019)

• Overall Survival (OS) [ Time Frame: Up to 5 years from randomization ]
• Pathologic Complete Response (pCR) Rate as Assessed by Blinded Independent Pathology Review (BIPR) [ Time Frame: At the time of surgery, between week 12 to week 18 ]
• Major Pathological Response (MPR) Rate as Assessed by Blinded Independent Pathology Review [ Time Frame: Up to 8 weeks following completion of neoadjuvant surgery, approximately study week 22 ]

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

Descriptive Information

• Brief Title: A Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Removal and Adjuvant Treatment With Nivolumab or Placebo for Participants With Surgically Removable Early Stage Non-small Cell Lung Cancer
• Official Title: A Phase 3, Randomized, Double-blind Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Resection and Adjuvant Treatment With Nivolumab or Placebo for Participants With Resectable Stage II-IIIB Non-small Cell Lung Cancer
• Brief Summary: The main purpose of the study is to examine if periadjuvant (neoadjuvant, then adjuvant) immunotherapy will prolong event free survival in participants with early stage non-small cell lung cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Biological: Nivolumab
  Specified dose on specified days
  Other Name: Opdivo, BMS936558
• Drug: Carboplatin
  Specified dose on specified days
• Drug: Cisplatin
  Specified dose on specified days
• Drug: Paclitaxel
  Specified dose on specified days
• Drug: Pemetrexed
  Specified dose on specified days
• Drug: Placebo
  Specified dose on specified days
• Drug: Docetaxel
  Specified dose on specified days

Study Arms

• Experimental: Neoadj. Nivo+ Pt-based Doublet Chemo followed by Adj. Nivo
  Interventions:

  • Biological: Nivolumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Pemetrexed
  • Drug: Docetaxel
• Placebo Comparator: Neoadj. Plac. + Pt-based Doublet Chemo followed by Adj.Plac.
  Interventions:

  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Pemetrexed
  • Drug: Placebo
  • Drug: Docetaxel

Publications *

• Leal TA, Ramalingam SS. Neoadjuvant therapy gains FDA approval in non-small cell lung cancer. Cell Rep Med. 2022 Jul 19;3(7):100691. doi: 10.1016/j.xcrm.2022.100691.
• Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, Levy R. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer. Cancer Res. 2022 Apr 1;82(7):1396-1408. doi: 10.1158/0008-5472.CAN-21-1382.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 9, 2024): 482
• Original Estimated Enrollment (submitted: July 17, 2019): 452
• Estimated Study Completion Date: September 30, 2024
• Actual Primary Completion Date: July 26, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants with suspected or histologically confirmed Stage IIA (> 4 cm) to IIIB (T3N2) non-small cell lung carcinoma (NSCLC) with disease that is considered resectable
• No brain metastasis
• Treatment-naive for NSCLC (no prior systemic anti-cancer treatment)
• Ability to provide surgical or biopsy tumor tissue for biomarkers
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1

Exclusion Criteria:

• Participants with an active, known or suspected autoimmune disease
• Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV)
• Any previous anti-cancer treatment including cytotoxic, IO treatment, targeted agents, or radiotherapy for NSCLC
• Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

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, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Ireland, Italy, Japan, Mexico, Netherlands, Poland, Puerto Rico, Romania, Russian Federation, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04025879
• Other Study ID Numbers: CA209-77T; 2019-000262-38 ( 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: April 2024