126O - Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) treatment for unresectable hepatocellular carcinoma (uHCC): CheckMate 9DW Asian subgroup analysis

Background

NIVO + IPI demonstrated statistically significant survival benefit vs LEN/SOR in patients (pts) with uHCC in the 1L setting (HR 0.79; 95% CI 0.65–0.96; P = 0.0180), with higher objective response rate (ORR), durable responses and manageable safety. We report outcomes for Asian pts from this preplanned interim analysis.

Methods

Adult pts with previously untreated HCC not eligible for curative surgical or locoregional therapies, Child-Pugh score 5–6, and ECOG performance status 0–1 were randomized 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (≤ 4 cycles) followed by NIVO 480 mg Q4W or investigator’s choice of LEN 8 or 12 mg QD or SOR 400 mg BID until disease progression or unacceptable toxicity. NIVO was given for a maximum of 2 years. The primary endpoint was overall survival (OS). Secondary endpoints included ORR and duration of response (DOR) by blinded independent central review per RECIST v1.1.

Results

Of 668 pts randomized globally, 280 were from Asia (NIVO + IPI, n = 133; LEN/SOR, n = 147); of 145 Asian pts treated with LEN/SOR, 137 (94%) received LEN. At 35.7 mo of median (m) follow-up in Asian pts, mOS was 34.0 mo with NIVO + IPI vs 22.5 mo with LEN/SOR (HR 0.75; 95% CI 0.54–1.03; Table); 24-mo OS rates were 54% vs 47%, respectively. ORR was 37% with NIVO + IPI vs 14% with LEN/SOR; mDOR was not reached (NR) vs 18.5 mo, respectively (Table). Any-grade treatment-related adverse events (TRAEs) occurred in 84% vs 94% of pts treated with NIVO + IPI vs LEN/SOR; grade 3/4 TRAEs occurred in 43% vs 45% of pts. Table: 126O

^aResponders only. NE, not estimable.

Conclusions

Consistent with the global study population, 1L NIVO + IPI showed improvements in mOS and ORR vs LEN/SOR, with durable responses and manageable safety in Asian pts with uHCC. These results further support NIVO + IPI as a potential new 1L therapy for uHCC.

Clinical trial identification

NCT04039607.

Editorial acknowledgement

Writing and editorial assistance were provided by Nitesh Sule, PhD, of Parexel.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

T. Yau: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, MSD Oncology, AstraZeneca. P.R. Galle: Financial Interests, Personal, Advisory Board: Bayer Schering , Sirtex Medical, Lilly, Bristol Myers Squibb, MSD, Roche/Genentech, Adaptimmune, Boston Scientific; Financial Interests, Personal, Speaker’s Bureau: Bayer Schering Pharma, Lilly, Roche, Ipsen; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Bayer Schering Pharma, Lilly, Sirtex Medical, AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Bayer Schering Pharma, Sirtex Medical, Roche/Genentech, Ipsen, Adaptimmune, MSD, AstraZeneca; Financial Interests, Personal, Research Funding: Roche/Genentech. T. Decaens: Financial Interests, Personal, Advisory Board: BMS, Bayer, Becton Dickinson, AstraZeneca, Ipsen, Roche, Sirtex, Terumo, Guerbet; Financial Interests, Personal, Invited Speaker: AbbVie, Gilead, MSD; Financial Interests, Institutional, Research Grant: ArQule, Guerbet, Genoscience Pharma. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Roche, Sirtex; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche. J. Park: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, AstraZeneca, Roche/Genentech, BeiGene; Financial Interests, Personal, Speaker’s Bureau: Bayer, Eisai, AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche/Genentech; Financial Interests, Institutional, Other: Genexine, Onconic Therapeutics, Eutilex; Financial Interests, Personal, Other, Honoraria: Bayer, Eisai, Ipsen, Roche/Genetech; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb Japan, Ono Pharmaceutical, AstraZeneca, Roche./Genentech, MSD, Exelixis, Eisai. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eisai, NIHON SERVIER, Novartis, Bristol Myers Squibb, MSD, Boehringer Ingelheim, Astellas Pharma, GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, NIHON SERVIER, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Fujifilm Toyama Chemical, Incyte Biosciences Japan, Takeda, Ono, MSD, Taisho Pharmaceutical, Nippon Kayaku, Guardant Health Japan, Nobelpharma, EA Pharma; Financial Interests, Institutional, Coordinating PI: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, MSD, Ono, Novartis, J-Pharma, Chiome Bioscience, NIHON SERVIER, Delta-Fly Pharma, Syneos Health, Merus.N.V., Merck biopharma, Boehringer Ingelheim, Invitae, Nobelpharma; Financial Interests, Personal, Steering Committee Member: Chugai, Nihon Servier, Takeda, Novartis, Eisai, Rakuten Medical. D.W.M. Tai: Financial Interests, Institutional, Advisory Board: Novartis, celgene, Sirtex, MSD, BMS, Eisai, Bayer, GSK. H.J. Chon: Financial Interests, Personal, Advisory Board: Eisai, Roche, Bayer, Ono, MSD, BMS, Sanofi, Servier, AstraZeneca, BeiGene; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Eisai, Bayer, BMS, Servier, Sanofi, Dong-A ST. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, Liscure. A. Hiraoka: Financial Interests, Personal, Invited Speaker: Chugai, AstraZeneca, Lilly. T. Yamashita: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Lilly, AstraZeneca; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, MSD, Ono, Abbie, Chugai, Eisai, AstraZeneca. T. Ogata: Financial Interests, Personal, Other, Part of compensation: Private; Financial Interests, Personal, Other, My private investment: Private. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Esai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. All other authors have declared no conflicts of interest.