65O - CheckMate 73L: Phase 3 study comparing nivolumab (N) + concurrent chemoradiotherapy (CCRT) followed by N _ ipilimumab (I) v CCRT followed by durvalumab (D) for previously untreated, locally advanced stage (stg) III NSCLC

Background

CCRT followed by D consolidation is the standard of care (SOC) for patients (pts) with unresectable stg III NSCLC; however, more than half of pts still have disease progression and die within 5 years. Dual IO with PD-(L)1 and CTLA-4 inhibitors has shown durable benefit in pts with metastatic NSCLC and may improve antitumor control as consolidation after CCRT in pts with unresectable stg III NSCLC. Here, we report final results from CheckMate 73L, a phase 3 study comparing N + CCRT followed by consolidation N + I or N v CCRT followed by D in this pt population.

Methods

Adults with untreated, unresectable stg III NSCLC and ECOG PS 0–1 were randomized 1:1:1 to receive N 360 mg Q3W + CCRT followed by up to 1 y of consolidation with N 360 mg Q3W + I 1 mg/kg Q6W (N + CCRT→N + I; Arm A) or consolidation with N 480 mg Q4W alone (N + CCRT→N; Arm B), or CCRT followed by up to 1 y of consolidation with D 10 mg/kg Q2W (CCRT→D; Arm C). The primary endpoint was PFS (RECIST v1.1 per BICR) comparing Arm A v C. Secondary endpoints included OS (Arm A v C and Arm B v C), PFS (Arm B v C), and safety.

Results

Overall, 287 pts were randomized to Arm A, 320 to Arm B, and 318 to Arm C; median follow-up was 30.5 mo (range 16.0–52.5 mo). Baseline characteristics were generally well-balanced across arms. N + CCRT→N + I did not show a statistically significant benefit in PFS v CCRT→D (median PFS 16.7 v 15.6 mo; HR [96% CI], 0.95 [0.77–1.19]; P=0.6461). Descriptive OS analysis showed no benefit with N + CCRT→N + I v CCRT→D (HR [95% CI], 1.12 [0.87–1.43]). PFS and OS were also not improved with N + CCRT→N v CCRT→D (0.84 [0.69–1.04]; 0.97 [0.76–1.24]). In Arms A, B, and C, respectively, rates for grade 3–4 treatment (tx)-related adverse events were 57%, 54%, and 49% (for pneumonitis were 4%, 4%, and < 1%) and tx-related deaths were 4%, 4%, and < 1%.

Conclusions

In CheckMate 73L, N + CCRT followed by N + I consolidation did not improve survival outcomes v SOC for pts with unresectable stg III NSCLC. No new safety signal was observed with N or I, although concurrent IO and CRT resulted in increased toxicity. These results emphasize the need to investigate novel efficacious tx options for pts with unresectable stg III NSCLC.

Clinical trial identification

NCT04026412.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Sara Thier, PhD, MPH, Samantha L. Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, Oncology Education, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: Hutchmed; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Coordinating PI, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Steering Committee Member, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Steering Committee Member, RELATIVITY 095: BMS; Financial Interests, Institutional, Steering Committee Member, BGB-A317-A1217-301/AdvanTIG-301: Beigene; Financial Interests, Institutional, Trial Chair, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Steering Committee Member, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Steering Committee Member, LAGOON: PharmaMar; Financial Interests, Institutional, Steering Committee Member, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Trial Chair, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Steering Committee Member, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche, Regeneron, Genmab; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Steering Committee Member: Novartis. D.E. Gerber: Financial Interests, Personal, Research Grant: AstraZeneca, BerGenBio, Karyopharm, Novocure; Financial Interests, Personal, Royalties: Oxford University Press; Financial Interests, Personal, Other, Consulting: Catalyst Pharmaceuticals; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, Daiichi Sankyo, Elevation Oncology, Janssen Scientific Affairs, Jazz Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi; Financial Interests, Personal, Other, Patent Issued: 11,747,345; Financial Interests, Personal, Other, Patent Pending: 17/045,482, 63/386,387, 63/382,972, 63/382,257; Financial Interests, Personal, Leadership Role, Chief Medical Officer: ncoSeer Diagnostics, Inc.; Financial Interests, Personal, Stocks/Shares: Gilead. S.S. Ramalingam: Financial Interests, Personal, Other, Editor in Chief, CANCER journal: American Cancer Society; Financial Interests, Personal, Research Grant: Merck, BMS, GSK; Financial Interests, Personal, Research Grant, Coordinating investigator for phase 3 trial: AstraZeneca, Amgen. A. Rittmeyer: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Daichi Sankyo, Gilead, GSK, MSD, Eli Lilly, Novartis, Pfizer, Roche. T. Ciuleanu: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics; Financial Interests, Personal, Other, speaker, consultancy, advisory board, principal investigator: Roche, Merck Sharp & Dohme, AstraZeneca, Pfizer, Bristol Myers Squibb, Eli Lilly, Amgen, Astellas, Novartis, Takeda; Financial Interests, Personal, Other, speaker, consultancy, advisory board: Janssen, Sandoz, Sanofi, Accord, Magna Pharm; Financial Interests, Personal, Other, Principal Investigator: Tesaro, Mirati, AbbVie, Celltrion; Financial Interests, Personal, Other, Principal Investigator: BeiGene. J. Menezes: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb. H.R. Kim: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Genentech/Roche; Financial Interests, Personal, Stocks/Shares: BridgeBio Therapeutics. C.I. Rojas: Financial Interests, Personal, Advisory Board: BMS, Roche, MSD, Pfizer, Sanofi; Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca, Knight, Pfizer; Financial Interests, Personal, Member of Board of Directors: Bradford Hill. K. Syrigos: Financial Interests, Personal, Other, Consulting Fees: Merck Sharp & Dohme, AstraZeneca, BMS, Amgen. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo K.K, Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Co. Ltd, Eli Lilly Japan K.K, Pfizer, AstraZeneca K.K, Daiichi Sankyo Co. Ltd; Financial Interests, Personal, Royalties, Currently no provided: Sysmex; Financial Interests, Personal, Steering Committee Member: Janssen Pharmaceutical K.K., GSK plc., Daiichi Sankyo, Inc.; Financial Interests, Institutional, Local PI: IQVIA Services Japan K.K, Syneos Health Clinical K.K., EPS Corporation., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., MSD K.K., Amgen Inc., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., CMIC CO., Ltd., Pfizer R&D Japan G.K., LabCorp Development Japan K.K., Kobayashi Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie Inc., A2 Healthcare Corp., Eli Lilly Japan K.K., Medpace Japan KK, EPS International Co., Ltd,., Covance Japan Inc., EP-CRSU CO., LTD., GSK K.K., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., PRA Health Sciences Inc., Astellas Pharma Inc., Ascent Development Services, AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Merck Biopharma Co., Ltd, Mochida Pharmaceutical Co., Ltd., Japan Clinical Research Operations; Financial Interests, Institutional, Research Grant: Japanese Gastric Cancer Association, Clinical Research Support Center Kyushu, Japan Clinical Cancer Research Organization, Ono Pharmaceutical Co., Ltd., Medical Research Support, Eisai Co., Ltd, Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bayer Yakuhin, Ltd, Kyowa Kirin Co., Ltd.; Financial Interests, Institutional, Funding: SRL MediSearch Inc., Eisai Inc., Thoracic Oncology Research Group(TORG), West Japan Oncology Group (WJOG), Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC), Mebix, Inc.; Non-Financial Interests, Personal, Member: West Japan Oncology Group, Japanese Society of Medical Oncology. A. Haridass: Financial Interests, Personal, Other, Speaker honoraria: AstraZeneca; Financial Interests, Personal, Other, Event registration fee and Speaker honoraria for lecture: BMS. R. Nathani: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. G. Pudussery: Financial Interests, Personal, Stocks/Shares: BMS. L. Yang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. D. De Ruysscher: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Philips Health, AstraZeneca; Financial Interests, Institutional, Coordinating PI: BMS, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Varian; Financial Interests, Personal, Funding: Olink; Financial Interests, Institutional, Funding: BeiGene; Financial Interests, Institutional, Other, Advise group brain metastases NSCLC: Eli Lilly. All other authors have declared no conflicts of interest.