A Study of Nivolumab and Ipilimumab in Untreated Participants With Stage 3 Non-small Cell Lung Cancer (NSCLC) That is Unable or Not Planned to be Removed by Surgery (CheckMate73L)

• ClinicalTrials.gov Identifier: NCT04026412
• Recruitment Status: Active, not recruiting
• First Posted: July 19, 2019
• Last Update Posted: January 25, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: July 18, 2019
• First Posted Date: July 19, 2019
• Last Update Posted Date: January 25, 2023
• Actual Study Start Date: October 8, 2019
• Estimated Primary Completion Date: July 7, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 30, 2021): Progression-free survival (PFS) by RECIST 1.1 per Blinded Independent Central Review (BICR) for Arm A vs Arm C [ Time Frame: Up to 7 years ]

Original Primary Outcome Measures (submitted: July 18, 2019)

• Progression Free Survival (PFS) Assessed by RECIST 1.1 per Blinded Independent Central Review (BICR) for Arm A and Arm C [ Time Frame: Up to 5 years ]
• Overall Survival (OS) for Arm A and Arm C [ Time Frame: Up to 5 years ]

Current Secondary Outcome Measures (submitted: November 30, 2021)

• Overall Survival (OS) for Arm A vs Arm C [ Time Frame: Up to 7 years ]
• PFS by RECIST 1.1 per BICR for Arm B vs Arm C [ Time Frame: Up to 7 years ]
• OS for Arm B vs Arm C [ Time Frame: Up to 7 years ]
• PFS by RECIST 1.1 per BICR for Arm A vs Arm B [ Time Frame: Up to 7 years ]
• OS for Arm A vs Arm B [ Time Frame: Up to 7 years ]
• Objective Response Rate (ORR) by RECIST 1.1 per BICR [ Time Frame: Up to 7 years ]
• Duration of Response (DoR) by RECIST 1.1 per BICR [ Time Frame: Up to 7 years ]
• Time to Response (TTR) by RECIST 1.1 per BICR [ Time Frame: Up to 7 years ]
• PFS by RECIST 1.1 per Investigator assessment [ Time Frame: Up to 7 years ]
• ORR by RECIST 1.1 per Investigator assessment [ Time Frame: Up to 7 years ]
• DoR by RECIST 1.1 per Investigator assessment [ Time Frame: Up to 7 years ]
• TTR by RECIST 1.1 per Investigator assessment [ Time Frame: Up to 7 years ]
• Time to Death or Distant Metastases (TTDM) by RECIST 1.1 per Investigator assessment [ Time Frame: Up to 7 years ]
• Incidence of Adverse Events (AEs) [ Time Frame: Up to 7 years ]
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: Up to 7 years ]
• Incidence of select AEs [ Time Frame: Up to 7 years ]
• Proportion of participants without symptom deterioration based on NSCLC-SAQ [ Time Frame: Up to 7 years ]
  Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ)

Original Secondary Outcome Measures (submitted: July 18, 2019)

• Overall Survival (OS) for Arm B and Arm C [ Time Frame: Up to 55 months ]
• Progression Free Survival (PFS) Assessed as per BICR for Arm B and Arm C [ Time Frame: Up to 40 months ]
• Objective Response Rate (ORR) and Complete Response Rate Assessed as per BICR [ Time Frame: Up to 7.5 years ]
• Duration of Response (DOR) Assessed as per BICR [ Time Frame: Up to 7.5 years ]
• Time to Response (TTR) Assessed as per BICR [ Time Frame: Up to 7.5 years ]
• Time to Death or Distant Metastases (TTDM) Assessed as per BICR [ Time Frame: Up to 7.5 years ]
• Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), and select AEs [ Time Frame: Up to 2 years ]
• Percentage of Participants Without Meaningful Symptom Deterioration Following 48 Weeks of Maintenance Therapy Based on Lung Cancer Subscale (LCS) of FACT-L and NSCLC-SAQ [ Time Frame: 48 Weeks ]

• 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 in Untreated Participants With Stage 3 Non-small Cell Lung Cancer (NSCLC) That is Unable or Not Planned to be Removed by Surgery
• Official Title: A Phase 3, Randomized, Open Label Study to Compare Nivolumab Plus Concurrent Chemoradiotherapy (CCRT) Followed by Nivolumab Plus Ipilimumab or Nivolumab Plus CCRT Followed by Nivolumab vs CCRT Followed by Durvalumab in Previously Untreated, Locally Advanced Non-small Cell Lung Cancer (LA NSCLC)
• Brief Summary: The primary purpose of the study is to compare the effectiveness of nivolumab plus concurrent chemoradiotherapy (CCRT) followed by nivolumab plus ipilimumab vs CCRT followed by durvalumab in participants with untreated Locally Advanced Non-small Cell Lung Cancer (LA NSCLC).
• 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 (NSCLC)

Intervention

• Biological: nivolumab
  Specified dose on specified days
• Biological: ipilimumab
  Specified dose on specified days
• Biological: durvalumab
  Specified dose on specified days

Study Arms

• Experimental: Arm A: nivolumab + CCRT + ipilimumab
  Concurrent chemoradiotherapy (CCRT)
  Interventions:

  • Biological: nivolumab
  • Biological: ipilimumab
• Experimental: Arm B: nivolumab + CCRT
  Concurrent chemoradiotherapy (CCRT)
  Intervention: Biological: nivolumab
• Experimental: Arm C: CCRT + durvalumab
  Concurrent chemoradiotherapy (CCRT)
  Intervention: Biological: durvalumab

• Publications *: De Ruysscher D, Ramalingam S, Urbanic J, Gerber DE, Tan DSW, Cai J, Li A, Peters S. CheckMate 73L: A Phase 3 Study Comparing Nivolumab Plus Concurrent Chemoradiotherapy Followed by Nivolumab With or Without Ipilimumab Versus Concurrent Chemoradiotherapy Followed by Durvalumab for Previously Untreated, Locally Advanced Stage III Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2022 May;23(3):e264-e268. doi: 10.1016/j.cllc.2021.07.005. Epub 2021 Jul 19.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: November 30, 2021): 888
• Original Estimated Enrollment (submitted: July 18, 2019): 1400
• Estimated Study Completion Date: December 3, 2026
• Estimated Primary Completion Date: July 7, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Locally advanced stage IIIA, IIIB, or IIIC (T1-2 N2-3 M0, T3 N1-3 M0, or T4 N0-3 M0) pathologically-confirmed NSCLC, according to 8th TNM classification. Participants who are not planned for potential curative surgical resection are eligible.
• Newly diagnosed and treatment-naïve, with no prior local or systemic anticancer therapy given as primary therapy for locally advanced disease

Exclusion Criteria:

• Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator would preclude the participant from adhering to the protocol or would increase the risk associated with study participation
• Active infection requiring systemic therapy within 14 days prior to randomization
• History of organ or tissue transplant that requires systemic use of immune suppressive agents
• Prior thoracic radiotherapy

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, Chile, China, France, Germany, Greece, Ireland, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Puerto Rico, Romania, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04026412
• Other Study ID Numbers: CA209-73L; 2019-001222-98 ( 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 2023