Abstract 933P
Background
In KEYNOTE-224 (NCT02702414), an open-label, single-arm, multicohort phase II study, pembro monotherapy showed antitumor activity and a manageable safety profile in both sorafenib-pretreated and treatment-naive advanced HCC. Here, we present updated results in patients (pts) with treatment-naive advanced HCC (cohort 2) based on an additional 6 months of follow-up.
Methods
Pts in cohort 2 had radiologically, histologically, or cytologically confirmed, incurable HCC not amenable or refractory to locoregional therapy, Child-Pugh A liver function, measurable disease based on RECIST 1.1 by BICR, ECOG PS 0-1, and BCLC stage C or B. Pts received pembro 200 mg IV Q3W for up to 2 years. Primary endpoint was ORR (RECIST 1.1 by BICR). Secondary endpoints included DOR, DCR, TTP, PFS, OS, and safety/tolerability.
Results
All 51pts enrolled in cohort 2 received ≥1 dose of pembro. The median time from the first dose to data cutoff (January 19, 2021) was 27 (range, 23-29) mo. ORR was 16% (95% CI, 7-29) and was similar across most subgroups. Median DOR was 16 (range, 3-24+) mo; 73% were estimated to have a response duration ≥12 mo per Kaplan-Meier estimate. Best overall responses were 0 CR, 8 (16%) PRs, 21 (41%) SDs, and 17 (33%) PDs; response was not evaluable or not assessed for 5 (10%) pts. DCR was 57%. The median TTP was 4 (95% CI, 3-9) mo. The median PFS was 4 (95% CI, 2-8) mo, and median OS was 17 (95% CI, 8-23) mo. PFS rate at 24 mo was 15%, and OS rate at 24 mo was 34%. No additional toxicity was observed since the last data cutoff, with treatment-related AEs (TRAEs) reported in 28 (55%) pts (grade ≥3, 16%). One treatment-related death occurred due to myocarditis, with associated immune-related hepatitis.
Conclusions
Similar to findings from cohort 1 of KEYNOTE-224 in the 2L setting, updated results from cohort 2 continued to demonstrate durable anti-tumor activity, promising OS, and manageable safety with no new safety signals for pembro monotherapy in pts with advanced HCC and no prior systemic therapy. These findings support further research of pembro-based regimens for the treatment of HCC.
Clinical trial identification
NCT02702414.
Editorial acknowledgement
Medical writing assistance was provided by Yue Liu of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
J. van Laethem: Financial Interests, Institutional, Research Grant: Merck & Co., Inc. M. Karwal: Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Research Grant: Eisai; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Merck & Co., Inc. C. Verslype: Financial Interests, Personal, Funding: Bayer; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Funding: Ipsen; Financial Interests, Personal, Speaker’s Bureau: Ipsen; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Funding: Lilly; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Role: Roche. H. Van Vlierberghe: Financial Interests, Institutional, Advisory Role: Merck & Co., Inc.; Financial Interests, Institutional, Research Grant: Merck & Co., Inc.; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Institutional, Advisory Role: Bayer; Financial Interests, Institutional, Advisory Role: Gilead; Financial Interests, Personal, Speaker’s Bureau: Gilead; Financial Interests, Institutional, Research Grant: Gilead; Financial Interests, Personal, Speaker’s Bureau: AbbVie; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Advisory Role: AbbVie; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Research Grant: Falk. A. Kardosh: Financial Interests, Personal, Advisory Role: Exelixis. V. Zagonel: Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Merck & Co., Inc.; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma; Financial Interests, Personal, Speaker’s Bureau: Servier; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Lilly. D. Sarker: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Research Grant: Eisai; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Research Grant: Ipsen; Financial Interests, Personal, Invited Speaker: Surface Oncology; Financial Interests, Personal, Research Grant: Surface Oncology; Financial Interests, Personal, Research Grant: AAA; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Funding: Merck Sharp & Dohme. D. Palmer: Financial Interests, Personal, Funding: MSD; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Funding: Sirtex; Financial Interests, Personal, Advisory Role: Sirtex; Financial Interests, Personal, Research Grant: Sirtex; Financial Interests, Personal, Funding: Nucana; Financial Interests, Personal, Advisory Role: Nucana; Financial Interests, Personal, Funding: Eisai; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Funding: Bayer. A. Vogel: Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Merck & Co., Inc.; Financial Interests, Personal, Advisory Role: Merck & Co., Inc.; Financial Interests, Personal, Speaker’s Bureau: Incyte; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Speaker’s Bureau: PierreFabre; Financial Interests, Personal, Advisory Role: PierreFabre; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Research Grant: Servier; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme. J. Edeline: Financial Interests, Personal, Research Grant: Eisai; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Ipsen; Financial Interests, Personal, Research Grant: Basilea; Financial Interests, Personal, Research Grant: Merck Serono; Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Sponsor/Funding: Beigene. S. Cattan: Financial Interests, Personal, Leadership Role: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Leadership Role: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Leadership Role: Ipsen; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Bayer. M. Kudo: Financial Interests, Personal, Advisory Role: Bayer AG; Financial Interests, Personal, Research Grant: Bayer AG; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Chugai Pharmaceutical Co; Financial Interests, Personal, Sponsor/Funding. Chugai Pharmaceutical Co; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical Co; Financial Interests, Personal, Funding: Bayer AG; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: EA Pharma Co; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Daiichi Sankyo Co; Financial Interests, Personal, Research Grant: Otsuka Pharmaceutical; Financial Interests, Personal, Research Grant: Sumitomo Dainippon Pharma; Financial Interests, Personal, Research Grant: Ono Pharmaceuticals; Financial Interests, Personal, Research Grant: Taiho Pharmaceutical. A. Cheng: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: Nucleix; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Research Grant: Roche/Genentech; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: CSR Pharma Group; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche; Financial Interests, Personal, Advisory Role: IQVIA; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Other: IQVIA. S. Ogasawara: Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Funding: Bayer; Financial Interests, Personal, Funding: Eisai; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Research Grant: Eisai; Financial Interests, Personal, Funding: Eli Lilly; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Funding: Chugai Pharma; Financial Interests, Personal, Advisory Role: Chugai Pharma; Financial Interests, Personal, Funding: Merck & Co., Inc.; Financial Interests, Personal, Research Grant: Merck & Co., Inc.; Financial Interests, Personal, Advisory Role: Merck & Co., Inc.; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca. A.B. Siegel: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. M. Chisamore: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. A. Wang: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. A. Zhu: Financial Interests, Personal, Research Grant: MSD. All other authors have declared no conflicts of interest.