Abstract 1255TiP
Background
Historically, the standard-of-care for patients (pts) with unresectable stage III NSCLC was CCRT; however, outcomes are poor with 5-y survival rates of 15–30%. While CCRT primes anti-tumour immunity, it also upregulates PD-L1 expression, potentially blunting any immune response. Thus, concurrent immunotherapy + CCRT may improve outcomes. The safety and tolerability of NIVO, an anti–PD-1 antibody, given concomitantly with CCRT in pts with stage III NSCLC was demonstrated in the phase 2 NICOLAS study (NCT02434081). Furthermore, combining NIVO with IPI, an anti–CTLA-4 antibody, resulted in a longer median overall survival (OS) versus chemotherapy in pts with advanced NSCLC who had a PD-L1 expression level of ≥1% in the phase 3 CheckMate 227 study (NCT02477826). In a prespecified exploratory analysis, NIVO + IPI showed an efficacy benefit versus NIVO. Previously, DURV, an anti–PD-L1 antibody, demonstrated significant improvements versus placebo in progression-free survival (PFS) and OS with manageable safety in pts without disease progression after CCRT in the phase 3 PACIFIC study (NCT02125461). Therefore, we will evaluate the efficacy of NIVO + CCRT followed by NIVO ± IPI versus CCRT followed by DURV for untreated, LA stage III NSCLC in the phase 3 randomized CheckMate 73L study (NCT04026412).
Trial design
In all, 888 pts aged ≥18 y with previously untreated stage III NSCLC and an ECOG PS ≤1 will be stratified by age, PD-L1 expression, and disease stage, then randomized (1:1:1) to receive NIVO (360 mg Q3W) + CCRT followed by NIVO (360 mg Q3W) + IPI (1 mg/kg Q6W; Arm A) or NIVO alone (480 mg Q4W; Arm B) for ≤1 y, or CCRT followed by DURV (10 mg/kg Q2W; Arm C) for ≤1 y. Pts with PD during CCRT will discontinue treatment and enter follow-up. Primary endpoints are PFS by RECIST 1.1, assessed by BICR (Arm A vs C) and OS (Arm A vs C). Secondary endpoints are PFS (Arm B vs A or C), OS (Arm B vs A or C), objective response rate, time to response, duration of response, time to distant metastases, and safety. Start date: Aug 2019.
Clinical trial identification
NCT04026412; July 19, 2019.
Editorial acknowledgement
Writing and editorial assistance was provided by Simon Wigfield, PhD, of Caudex, funded by Bristol-Myers Squibb Company.
Legal entity responsible for the study
Bristol-Myers Squibb Company.
Funding
Bristol-Myers Squibb Company.
Disclosure
D. De Ruysscher: Honoraria (institution): Bristol-Myers Squibb Company, Celgene, Merck/Pfizer, Roche/Genentech, AstraZeneca, MSD, Seattle Genetics; Advisory/Consultancy, To institution: Bristol-Myers Squibb Company, Celgene, Merck/Pfizer, Roche/Genentech, AstraZeneca, MSD, Seattle Genetics; Research grant/Funding (institution): Boehringer Ingelheim, Bristol-Myers Squibb Company. AstraZeneca, Philips, Olink. S.S. Ramalingam: Advisory/Consultancy: Amgen, AbbVie, Bristol-Myers Squibb Company, Genentech/Roche, Merck, AstraZeneca, Takeda; Research grant/Funding (institution): Advaxis, Amgen, AstraZeneca, Bristol-Myers Squibb Company, Merck, Takeda, Tesaro. D.E. Gerber: Advisory/Consultancy: Catalyst Pharmaceuticals; Research grant/Funding (institution): AstraZeneca, BerGenBio, Karyopharm, 3V Biosciences; Shareholder/Stockholder/Stock options: Gilead; Non-remunerated activity/ies: Bristol-Myers Squibb Company, Karyopharm. D.S.W. Tan: Honoraria (self): Boehringer Ingelheim, Merck, Roche, Pfizer, Novartis, Takeda; Advisory/Consultancy: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli Lilly, Loxo, Pfizer, Takeda, Merrimack; Research grant/Funding (self): Novartis, Bayer, AstraZeneca, GlaxoSmithKline, Pfizer; Travel/Accommodation/Expenses: Pfizer, Takeda, Boehringer Ingelheim, Novartis, Merck. J. Cai: Full/Part-time employment: Bristol-Myers Squibb Company. A. Li: Full/Part-time employment: Bristol-Myers Squibb Company. S. Peters: Honoraria (institution), Advisory/Consultancy: AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Bioinvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp & Dohme Corp., M; Research grant/Funding (institution): Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche, Illumina, Merck Sharp & Dohme Corp., Merck Serono, Novartis, Pfizer; Travel/Accommodation/Expenses, Travel for adboards/meetings: AstraZeneca, Bayer, Bristol-Myers Squibb, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Merck Sharp & Dohme Corp., Pfizer, Seattle Genetics. All other authors have declared no conflicts of interest.