965MO - Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) treatment for unresectable hepatocellular carcinoma (uHCC): Expanded analyses from CheckMate 9DW

Background

In the phase 3 CheckMate 9DW study, 1L NIVO + IPI demonstrated statistically significant and clinically meaningful overall survival (OS) benefit vs LEN/SOR in patients (pts) with uHCC (NCT04039607). We present additional exploratory analyses from this preplanned interim analysis.

Methods

Pts with previously untreated HCC not eligible for curative surgical or locoregional therapies, Child-Pugh score 5 or 6, and ECOG performance status 0 or 1 were randomized 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (up to 4 cycles; then NIVO 480 mg Q4W) or LEN 8 mg 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 OS; secondary endpoints included objective response rate (ORR) and duration of response (DOR) per blinded independent central review (BICR) using RECIST v1.1.

Results

A total of 668 pts were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333). At a median follow-up of 35.2 (range 26.8–48.9) months (mo), median OS was 23.7 (95% CI 18.8–29.4) mo with NIVO + IPI vs 20.6 (95% CI 17.5–22.5) mo with LEN/SOR (HR 0.79; 95% CI 0.65–0.96; P = 0.0180); 24-mo OS rates were 49% (95% CI 44–55) vs 39% (95% CI 34–45), respectively. OS benefit was generally consistent across pt subgroups. ORR was higher with NIVO + IPI vs LEN/SOR (36% [95% CI 31–42] vs 13% [95% CI 10–17]; P < 0.0001), with higher complete response rates (7% vs 2%) and durable responses (median DOR: 30.4 [95% CI 21.2–not estimable] vs 12.9 [95% CI 10.2–31.2] mo). Any-grade treatment-related adverse events (TRAEs) were reported in 84% of pts with NIVO + IPI vs 91% of pts with LEN/SOR; grade 3–4 TRAEs were reported in 41% vs 42% of pts, respectively. Additional exploratory efficacy and safety analyses will be presented.

Conclusions

In pts with previously untreated uHCC, NIVO + IPI demonstrated statistically significant OS benefit vs LEN/SOR, with higher ORR and durable responses, along with manageable safety. These results further support NIVO + IPI as a potential 1L treatment option for uHCC.

Clinical trial identification

NCT04039607.

Editorial acknowledgement

Writing and editorial assistance were provided by Dhivya Ramalingam, PhD, of Parexel.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

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. T. Yau: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, MSD Oncology, AstraZeneca. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Takeda, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Chugai, Eisai, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. B. Sangro: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, AstraZeneca, Bayer, Sirtex Medical, Roche/Genentech, Eisai, Incyte, Boston Scientific, Sanofi Pasteur; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eisai, Incyte, Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Bristol Myers Squibb, Sirtex Medical, Eisai, Roche; Financial Interests, Personal, Research Funding: Bristol Myers Squibb, Roche. L. Da Fonseca: Financial Interests, Personal, Advisory Board: Bayer, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Knight Pharmaceuticals, Bayer, Roche, AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Roche; Financial Interests, Personal, Other, Honoraria: Bayer, AstraZeneca, Roche, Knight Pharmaceuticals, BMS Brazil; Financial Interests, Personal, Research Funding: Bayer. H. Karachiwala: Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Roche Canada, Eisai, Merck, BMS, Incyte, Ipsen, AstraZeneca, Amgen, Astella Pharma, Takeda. J. Park: Financial Interests, Personal, Advisory Board: 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, Other Relationship: Genexine, Onconic Therapeutics, Eutilex; Financial Interests, Personal, Other, Honoraria: Bayer, Eisai, Ipsen, Roche/Genentech; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Ono Pharmaceuticals, AstraZeneca, Roche/Genentech, MSD, Exelixis, Eisai. D.W.M. Tai: Financial Interests, Institutional, Advisory Board: Novartis, Celgene, Sirtex, MSD, BMS, Eisai, Bayer, GSK. A. Santoro: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, Incyte; Financial Interests, Personal, Speaker’s Bureau: Takeda, Roche, AbbVie, Amgen, Celgene, AstraZeneca, Lilly, Sandoz, Novartis, Bristol Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, ArQule. G. Pizarro: Financial Interests, Personal, Speaker’s Bureau: Bayer, Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bayer, Pfizer; Financial Interests, Personal, Expert Testimony: Bayer, Pfizer; Financial Interests, Personal, Other, Honoraria: Bayer, Pfizer. M. Schenker: Financial Interests, Personal and Institutional, Local PI, Payment for Clinical trials activities: B.M.S., M.S.D., Roche, Merck Serono, Sanofi, Regeneron, AstraZeneca, Pfizer, G.S.K, Novartis, Astellas, PharmaMar, BeiGene, Clovis Pharmaceutical, AbbVie, Bioven, Mylan, Samsung Pharmaceutical, Eisai, Gilead, Amgen, Daiichi Sankyo. A.R. He: Financial Interests, Personal, Invited Speaker, Speaker's Bureau: Eisai; Financial Interests, Personal, Invited Speaker, Speaker's bureau: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca. T. Ogata: Financial Interests, Personal, Stocks/Shares, Part of compensation: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership, My private investment: Bristol Myers Squibb. P.R. Galle: Financial Interests, Personal, Advisory Board: Bayer Schering Pharma, 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, Accommodations, Expenses: Bayer Schering Pharma, Lilly, Sirtex Medical, AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bayer Schering Pharma, Bristol Myers Squibb, Sirtex Medical, Roche/Genentech, Ipsen, Adaptimmune, MSD, AstraZeneca/MedImmune; Financial Interests, Personal, Research Funding: Roche/Genentech. All other authors have declared no conflicts of interest.