68P A phase Ib study of lenvatinib + pembrolizumab (LEN + PEMBRO) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Study 116 follow-up analysis

Abstract

BackgroundIn Study 116, LEN + PEMBRO demonstrated promising efficacy in pts with uHCC (n = 100) at data cutoff, October 31, 2019. Of note, median overall survival (OS) was 22 mos (95% CI 20.4–not estimable [NE]). Here, we present results from follow-up survival analyses performed 17 mos after the original data cutoff.MethodsOS was assessed at a cutoff date of March 31, 2021; best response (BR) was assessed at August 7, 2020 per independent imaging review (IIR) and at March 31, 2021 per investigator assessment (Inv). OS, progression-free survival (PFS), and duration of response (DOR) were estimated using the Kaplan-Meier method. Landmark analyses of OS were conducted for pts alive at 3 and 9 mos from first dose and classified by pts’ BR up to 3 and 9 mos.ResultsAt data cutoff (March 31, 2021) with a median follow-up time of 27.6 mos, 38 pts (38%) were alive, and 2 pts (2%) had withdrawn consent. ORR was 43.0% (95% CI 33.1–53.3) with a median DOR of 17.1 mos (95% CI 6.9–19.3) and median PFS was 9.3 mos (95% CI 7.4–9.8), all by mRECIST per Inv. The median OS was 20.4 mos (95% CI 14.4–25.9). Landmark analyses at 3 and 9 mos suggested an association between BR and OS in pts treated with LEN + PEMBRO (Table). Landmark analyses by IIR via mRECIST or RECIST 1.1 were comparable to those by Inv via mRECIST (Table). Of 79 pts evaluable for immunogenicity, 0 pts had treatment-emergent anti-drug antibodies (ADA); 3 pts had non-treatment-emergent ADAs. PEMBRO exposure was comparable for ADA positive and negative pts treated with the same regimen.ConclusionsTable: 68PLandmarkmRECIST, per InvmRECIST, per IIRRECIST 1.1, per IIRnMedian OS (mos) (95% CI)nMedian OS (mos) (95% CI)nMedian OS (mos) (95% CI)BR, 3 mosCR/PR3025.9 (18.0 - NE)3627.6 (18.3 - NE)22NE (22.8 - NE)SD5621.2 (14.3 - NE)5220.4 (13.4 - NE)6619.4 (13.4 - 25.9)PD/Not evaluable75.2 (3.0 - 9.9)55.2 (3.0 - 8.6)54.6 (3.0 - 7.9)BR,* 9 mosCR/PR33NE (25.9 - NE)42NE (22.0 - NE)33NE (25.9 - NE)SD3523.7 (18.6 - NE)2825.9 (18.6 - NE)3721.5 (17.0 - NE)*Tumor responses were not evaluable for 2 pts by mRECIST per Inv.BR, best response; CR, complete response; NE, not estimable; PD, progressive disease; PR, partial response; SD, stable disease.Data cutoff: March 31, 2021 (except BR per IIR: August 7, 2020). Open table in a new tab Clinical trial identificationNCT03006926.Editorial acknowledgementMedical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Legal entity responsible for the studyEisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.FundingEisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.DisclosureM. Kudo: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Other, Honoria : MSD; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honora: Bayer; Financial Interests, Personal, Other, Honoraria: Lilly Japan; Financial Interests, Personal, Other, Honoraria: EA Pharma; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb Japan; Financial Interests, Institutional, Research Grant: Otsuka; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Gilead Sciences; Financial Interests, Institutional, Research Grant: EA Pharma; Financial Interests, Institutional, Research Grant: Sumitomo Dainippon Pharma; Financial Interests, Personal, Research Grant: Ono Pharmaceutical. 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M. Ikeda: Financial Interests, Personal, Advisory Role: Bayer Yakuhin; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Lilly Japan; Financial Interests, Personal, Advisory Role: Chugai Pharma; Financial Interests, Personal, Advisory Role: Micron; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Bayer Yakuhin; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Lilly Japan; Financial Interests, Personal, Other, Honoraria: Sumitomo Dainippon Pharma; Financial Interests, Personal, Other, Honoraria: Teijin Pharma; Financial Interests, Personal, Other, Honoraria: EA Pharma; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Mylan; Financial Interests, Personal, Other, Honoraria: Otsuka; Financial Interests, Personal, Other, Honoraria: Yakult Pharmaceutical; Financial Interests, Personal, Other, Honoraria: SERVIER; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Chugai Pharma; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Bayer Yakuhin; Financial Interests, Institutional, Research Grant: Yakult Pharmaceutical; Financial Interests, Institutional, Research Grant: Lilly Japan; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Chugai Pharma; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: ASLAN Pharmaceuticals; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: J-Pharma; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Nobelpharma; Financial Interests, Institutional, Research Grant: Delta-Fly Pharma; Financial Interests, Institutional, Research Grant: Chiome Bioscience; Financial Interests, Institutional, Research Grant: Merus NV. 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Baron: Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Johnson & Johnson; Financial Interests, Personal, Speaker’s Bureau: Exelixis; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma. T. 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Kaneko: Financial interests, Insitutional, Research Grant:Gilead Sciences, AbbVie, Daiichi Sankyo, Astellas Pharma, Bayer, Takeda, Nippon Boehringer Ingelheim, MSD, Ono Pharma, Pfizer, Shionogi, Teijin Pharma, Mitsubishi Tanabe, Zeria, Abbott Vascular Japan, Taisho Toyama, Novartis, Terumo Corporation, Taiho, Novo Nordisk, Bayer, Mylan, Kyowa Hakko Kirin, Otsuka, Medtronic Japan, Sanwa Kagaku Kenkyusho, Sanofi, Boston Scientific Japan, Nippon Kayaku, St. Jude Medical Japan, Alexion Pharma, Central Medical, Kowa, Lilly, Nihon Medi-Physics, Japan Lifeline, Biotronik Japan, Zeon Medical, Tomiki Medical Instruments, Eisai Inc, Aska Pharma, Bristol-Myers, Kataoka, Sumitomo Dainippon, EA Pharma; Financial interests, Personal, Advisory Role: Bayer, Kowa, Hokkoku, Lily; Financial interests, Personal, Honoraria: EA Pharma, MSD, Aska Pharma, Astellas Pharma, AbbVie, Eisai Inc, Eidia, Otsuka, Gilead Sciences, Sysmex Corporation, Daiichi Sankyo, Taisho Toyama, Sumitomo Dainippon, Taiho, Takeda, Chugai, Bayer, Bristol Myers, Mylan EPD, Miyarisan, Mochida, Kowa, Mitsubishi Tanabe Pharma, Lilly. 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BackgroundIn Study 116, LEN + PEMBRO demonstrated promising efficacy in pts with uHCC (n = 100) at data cutoff, October 31, 2019. Of note, median overall survival (OS) was 22 mos (95% CI 20.4–not estimable [NE]). Here, we present results from follow-up survival analyses performed 17 mos after the original data cutoff. In Study 116, LEN + PEMBRO demonstrated promising efficacy in pts with uHCC (n = 100) at data cutoff, October 31, 2019. Of note, median overall survival (OS) was 22 mos (95% CI 20.4–not estimable [NE]). Here, we present results from follow-up survival analyses performed 17 mos after the original data cutoff. MethodsOS was assessed at a cutoff date of March 31, 2021; best response (BR) was assessed at August 7, 2020 per independent imaging review (IIR) and at March 31, 2021 per investigator assessment (Inv). OS, progression-free survival (PFS), and duration of response (DOR) were estimated using the Kaplan-Meier method. Landmark analyses of OS were conducted for pts alive at 3 and 9 mos from first dose and classified by pts’ BR up to 3 and 9 mos. OS was assessed at a cutoff date of March 31, 2021; best response (BR) was assessed at August 7, 2020 per independent imaging review (IIR) and at March 31, 2021 per investigator assessment (Inv). OS, progression-free survival (PFS), and duration of response (DOR) were estimated using the Kaplan-Meier method. Landmark analyses of OS were conducted for pts alive at 3 and 9 mos from first dose and classified by pts’ BR up to 3 and 9 mos. ResultsAt data cutoff (March 31, 2021) with a median follow-up time of 27.6 mos, 38 pts (38%) were alive, and 2 pts (2%) had withdrawn consent. ORR was 43.0% (95% CI 33.1–53.3) with a median DOR of 17.1 mos (95% CI 6.9–19.3) and median PFS was 9.3 mos (95% CI 7.4–9.8), all by mRECIST per Inv. The median OS was 20.4 mos (95% CI 14.4–25.9). Landmark analyses at 3 and 9 mos suggested an association between BR and OS in pts treated with LEN + PEMBRO (Table). Landmark analyses by IIR via mRECIST or RECIST 1.1 were comparable to those by Inv via mRECIST (Table). Of 79 pts evaluable for immunogenicity, 0 pts had treatment-emergent anti-drug antibodies (ADA); 3 pts had non-treatment-emergent ADAs. PEMBRO exposure was comparable for ADA positive and negative pts treated with the same regimen. At data cutoff (March 31, 2021) with a median follow-up time of 27.6 mos, 38 pts (38%) were alive, and 2 pts (2%) had withdrawn consent. ORR was 43.0% (95% CI 33.1–53.3) with a median DOR of 17.1 mos (95% CI 6.9–19.3) and median PFS was 9.3 mos (95% CI 7.4–9.8), all by mRECIST per Inv. The median OS was 20.4 mos (95% CI 14.4–25.9). Landmark analyses at 3 and 9 mos suggested an association between BR and OS in pts treated with LEN + PEMBRO (Table). Landmark analyses by IIR via mRECIST or RECIST 1.1 were comparable to those by Inv via mRECIST (Table). Of 79 pts evaluable for immunogenicity, 0 pts had treatment-emergent anti-drug antibodies (ADA); 3 pts had non-treatment-emergent ADAs. PEMBRO exposure was comparable for ADA positive and negative pts treated with the same regimen. ConclusionsTable: 68PLandmarkmRECIST, per InvmRECIST, per IIRRECIST 1.1, per IIRnMedian OS (mos) (95% CI)nMedian OS (mos) (95% CI)nMedian OS (mos) (95% CI)BR, 3 mosCR/PR3025.9 (18.0 - NE)3627.6 (18.3 - NE)22NE (22.8 - NE)SD5621.2 (14.3 - NE)5220.4 (13.4 - NE)6619.4 (13.4 - 25.9)PD/Not evaluable75.2 (3.0 - 9.9)55.2 (3.0 - 8.6)54.6 (3.0 - 7.9)BR,* 9 mosCR/PR33NE (25.9 - NE)42NE (22.0 - NE)33NE (25.9 - NE)SD3523.7 (18.6 - NE)2825.9 (18.6 - NE)3721.5 (17.0 - NE)*Tumor responses were not evaluable for 2 pts by mRECIST per Inv.BR, best response; CR, complete response; NE, not estimable; PD, progressive disease; PR, partial response; SD, stable disease.Data cutoff: March 31, 2021 (except BR per IIR: August 7, 2020). Open table in a new tab *Tumor responses were not evaluable for 2 pts by mRECIST per Inv. BR, best response; CR, complete response; NE, not estimable; PD, progressive disease; PR, partial response; SD, stable disease. Data cutoff: March 31, 2021 (except BR per IIR: August 7, 2020). Clinical trial identificationNCT03006926. NCT03006926. Editorial acknowledgementMedical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Medical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Legal entity responsible for the studyEisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. FundingEisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.