Abstract 713P
Background
Pembro demonstrated promising ORR in sorafenib-treated patients (pts) with aHCC in KEYNOTE-224, leading to accelerated regulatory approval in the US. KEYNOTE-240 showed a similar ORR and clinically meaningful improvements in OS and PFS, although prespecified statistical significance criteria for OS and PFS were narrowly missed. KEYNOTE-394 demonstrated statistically significant and clinically meaningful benefit in OS, PFS, and ORR with pembro vs pbo in pts from Asia with sorafenib or oxaliplatin-based chemotherapy treated aHCC. Data from KEYNOTE-240 after 4.5 years of follow-up are reported.
Methods
Pts with sorafenib-treated aHCC were randomized 2:1 to pembro 200 mg IV Q3W or pbo. Dual primary end points were OS and PFS, assessed by blinded independent central review (BICR) per RECIST v1.1. Secondary end points were ORR, DOR, DCR, TTP (all assessed by BICR per RECIST v1.1), and safety.
Results
As of 8/22/2021, median (range) time from randomization to data cutoff was 53.9 (46.1-63.1) mo for pembro and 54.1 (46.0-62.2) mo for pbo. Median (95% CI) OS was 13.9 (11.6-16.0) mo for pembro and 10.6 (8.3-13.5) mo for pbo (HR, 0.774; 95% CI, 0.623-0.963). Estimated OS rates at 36 and 48 mo for pembro and pbo were 17.9% and 11.1% and 13.0% and 6.6%, respectively. Median (95% CI) PFS was 3.0 (2.8-4.1) mo for pembro and 2.8 (1.6-3.0) mo for pbo (HR, 0.726; 95% CI, 0.577-0.913). Estimated PFS rates at 36 and 48 mo for pembro and pbo were 8.6% and 0% and 5.0% and 0%, respectively. ORR (95% CI) was 18.3% (14.0-23.4) for pembro and 4.4% (1.6-9.4) for pbo. Median (range) DOR was 13.9 (1.5+ to 51.0+) mo for pembro and 15.2 (2.8-21.9) mo for pbo. DCR was 63.3% for pembro and 55.6% for pbo. Median (95% CI) TTP was 3.8 (2.8-4.4) mo for pembro and 2.8 (1.6-3.0) mo for pbo. No new or unexpected adverse events occurred.
Conclusions
With extended follow-up from KEYNOTE-240, pembro continued to provide improvement in OS and PFS and had a manageable safety profile vs pbo in pts with sorafenib-treated aHCC. These data, together with findings from KEYNOTE-224 and KEYNOTE-394, reinforce the long-term efficacy and favorable benefit-risk profile of pembro in the aHCC setting.
Clinical trial identification
NCT02702401 Release date: March 8, 2016.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Lauren D’Angelo, PhD of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
J. Edeline: Financial Interests, Personal, Invited Speaker: MSD, Eisai, BMS, AstraZeneca, Bayer, Roche, Ipsen, Basilea, Merck Serono, Incyte, Servier, Beigene; Financial Interests, Personal, Other, Travel: Amgen; Financial Interests, Institutional, Funding: BMS, Beigene. R.S. Finn: Financial Interests, Institutional, Research Grant: Adaptimmune, Bayer, Pfizer, Eisai, Roche, Merck, Genentech, BMS, Eli Lilly; Financial Interests, Personal, Other, Personal consultancy fees: Adpatimmune, AstraZeneca, Eisai, CStone, Merck BMS, Bayer, Exilixis, Roche/ Genentech, Pfizer, Eli Lilly. M. Bouattour: Financial Interests, Personal, Invited Speaker: Bayer, Sirtex Medical, Roche, BMS, Ipsen; Financial Interests, Personal, Advisory Board: Bayer, Sirtex Medical, Roche, BMS,. A. Cheng: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Bayer Healthcare, AstraZeneca, Genentech/Roche, Merck Sharp Dohme, BeiGene, Ltd., EXELIXIS Ltd., Ipsen Innovation, F. Hoffmanna-La Roche Ltd; Financial Interests, Personal, Invited Speaker: Eisai, Ono Pharmaceutical, Bayer Yakuhin Ltd., Novartis, Amgen Taiwan, Chugai Pharmaceutical; Financial Interests, Personal, Other, Travel: IQVIA. S.L. Chan: Financial Interests, Personal, Funding: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, MSD, BMS, Roche. T. Yau: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, MSD, Exelixis, Ipsen, Eisai, AstraZeneca, Bayer, Novartis, EMD Sereon, Abbvie, Pfizer, Eli Lilly, Sirtex, Sillajen, Taiho, OrigiMed, New B Innovation, Sirtex, H3 Biomedicine; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, MSD, Exelixis, Ipsen, Eisai, AstraZeneca, Bayer, Novartis, EMD Sereon, Abbvie, Pfizer, Eli Lilly, Sirtex, Sillajen, Taiho, OrigiMed, New B Innovation, Sirtex, H3 Biomedicine. M. Garrido: Financial Interests, Personal, Invited Speaker: BMS, MSD, Pfizer; Financial Interests, Personal, Advisory Board: BMS, MSD, Pfizer; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Principal Investigator: BMS, MSD; Financial Interests, Personal, Expert Testimony: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Personal and Institutional, Invited Speaker: Merck; Financial Interests, Personal and Institutional, Advisory Board: Merck; Financial Interests, Personal and Institutional, Research Grant: Merck. J. Knox: Financial Interests, Personal, Advisory Board, advisor on HB portfolio and trials.: AstraZeneca; Non-Financial Interests, Principal Investigator, Emerald 2. ( not compensated): AstraZeneca; Non-Financial Interests, Principal Investigator, Nutide trial: Nucana. B. Daniele: Financial Interests, Personal, Invited Speaker: Eisai, Ipsen, Roche; Financial Interests, Personal, Writing Engagements: Eisai, Ipsen; Financial Interests, Personal, Advisory Board: Eisai, Ipsen, AstraZeneca, Roche, Lilly, Amgen, Bayer, Sanofi, MSD. V. Breder: Financial Interests, Personal, Invited Speaker: MSD, Roche, Bayer, AstraZeneca, Eisai, BMS; Financial Interests, Personal, Advisory Board: MSD, Roche, Bayer, AstraZeneca, Eisai, BMS; Financial Interests, Personal, Principal Investigator: MSD, Roche, AstraZeneca, Eisai, BMS; Financial Interests, Personal, Advisory Role: MSD, Roche, Bayer, AstraZeneca, Eisai, BMS. H.Y. Lim: Non-Financial Interests, Personal, Invited Speaker: Bayer; Non-Financial Interests, Personal, Advisory Board: Bayer, Eisai, Roche, BMS, Ipsen; Non-Financial Interests, Personal, Principal Investigator: Bayer, Eisai, Roche. A. Odeleye-Ajakaye: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.. I. Martinez-Forero: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. A.B. Siegel: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.. P. Merle: Financial Interests, Personal and Institutional, Advisory Board: Roche, AstraZeneca, MSD, Eisai, Bayer, Ipsen; Financial Interests, Personal, Research Grant: Ipsen. All other authors have declared no conflicts of interest.