Abstract 1396
Background
LEN is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT. PEMBRO is an anti-PD-1 monoclonal antibody. LEN monotherapy is approved for first-line treatment of uHCC. PEMBRO monotherapy has shown significant efficacy in the second-line treatment of HCC. We report updated results from a phase 1b trial of LEN + PEMBRO in uHCC.
Methods
In this open-label, phase 1b study of LEN + PEMBRO in uHCC, 104 patients (pts) with BCLC stage B (not amenable for transarterial chemoembolization) or C, Child-Pugh class A, and ECOG PS ≤ 1 received LEN (body wt ≥ 60 kg: 12 mg/day; <60 kg: 8 mg/day QD) and PEMBRO (200 mg IV Q3W). Primary endpoints were safety (DLT part) and efficacy (expansion part; objective response rate [ORR] and duration of response [DOR]). Investigators performed tumor assessments using modified RECIST for HCC. No dose-limiting toxicities (DLTs) were reported in the DLT part (n = 6). Enrollment was expanded to approximately 100 pts (expansion part). Recruitment (N = 104) was completed April 2019. We present results for the first 67 pts enrolled by December 31, 2018.
Results
Pts received LEN + PEMBRO (DLT-evaluation part, n = 6; expansion part, n = 61). At data cutoff (June 30, 2019), 34 (50.7%) pts remained on study treatment; median duration of follow-up was 11.7 months (95% CI, 7.8-17.6). Serious adverse events occurred in 42 (62.7%) pts; no new safety signals emerged. Updated safety data will be provided. ORR (including unconfirmed responses) was 44.8% (Table) and compared favorably with LEN arm of REFLECT trial (24.1%; Kudo M. Lancet. 2018). Median DOR was 18.7 months (95% CI, 6.9-NE).
Conclusions
LEN + PEMBRO showed promising antitumor activity and an acceptable safety profile in pts with uHCC. Blinded independent central review is in progress. A phase 3 trial (LEAP-002; NCT03713593) is ongoing to assess LEN + PEMBRO vs LEN alone as first-line therapy for pts with uHCC.Table:
747P
Response Parameter, n (%) | LEN + PEMBRO (n = 67) |
---|---|
mRECIST Per Investigator | |
ORR (CR + PR + unconfirmed PR or CR)a Best Overall Response CR. PRa Stable disease Progressive disease Unknown/not evaluable | 30 (44.8)
4 (6.0) 26 (38.8) 25 (37.3) 6 (9.0) 6 (9.0) |
Includes unconfirmed partial responses (2 patients). CR, complete response; (m)RECIST, (modified) Response Evaluation Criteria In Solid Tumors [Lencioni et al. Semin Liver Dis. 2010;30:52-60]; ORR, objective response rate; PR, partial response.
Clinical trial identification
NCT03006926; Release date: December 30, 2016.
Editorial acknowledgement
Medical writing support was provided by April Suriano, PhD, of Oxford PharmaGenesis, Newtown, PA, USA and was funded by Eisai Inc.
Legal entity responsible for the study
Eisai Inc.
Funding
Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
J. Llovet: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy, Research grant / Funding (self): Eisai; Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): Ipsen; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celsion Corporation; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Merck; Advisory / Consultancy: Glycotest; Advisory / Consultancy: Navigant; Advisory / Consultancy: Leerink Swann LLC; Advisory / Consultancy: Midatech Ltd; Advisory / Consultancy: Fortess Biotech; Advisory / Consultancy: Sprink Pharmaceuticals; Advisory / Consultancy: Nucleix; Advisory / Consultancy: Can-Fite Biopharma. K.V. Shepard: Full / Part-time employment: Eisai Inc. R.S. Finn: Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer. M. Ikeda: Honoraria (self): Abbott, Bayer, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Eisai, Lilly, Nobelpharma, Novartis, Otsuka, Taiho Pharmaceutical, Teijin Pharma, Yakult Honsha; Advisory / Consultancy: Bayer, Daiichi Sankyo, Eisai, Kyowa Hakko Kirin, MSD, NanoCarrier, Novartis, Shire, Teijin Pharma, Lilly; Research grant / Funding (self): ASLAN Pharmaceuticals, AstraZeneca, Baxalta/Shire, Bayer, Bristol-Myers Squibb, Chugai Pharma, Eisai, Kowa, Kyowa Hakko Kirin, Lilly, Merck Serono, MSD, NanoCarrier, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical, Takara Bio, Yakult Honsha. M. Sung: Advisory / Consultancy: Bayer; Advisory / Consultancy: Eisai; Advisory / Consultancy: Exelixis. A.D. Baron: Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Genentech/Roche; Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Merck. M. Kudo: Honoraria (self), Research grant / Funding (self): AbbVie; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self): EA Pharma; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self): Gilead Sciences; Honoraria (self): Merck Serono; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (self): Taiho Pharmaceutical; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): Chugai Pharma; Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): Otsuka. T. Okusaka: Honoraria (self): AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Chugai Pharma, Daiichi Sankyo, EA Pharma, Eisai, Fujifilm, Lilly Japan, Nippon Chemiphar, Nobelpharma, Novartis, Ono Pharmaceutical, Pfizer, Sumitomo Dainippon, Taiho Pharmaceutical, Teijin Pharma, Yakult; Advisory / Consultancy: Daiichi Sankyo, Sumitomo Dainippon, Taiho Pharmaceutical, Zeria Pharmaceutical; research funding from AstraZeneca, Baxter, Bayer, Chugai Pharma, Dainippon Sumitomo Pharma, Eisai, Kowa, Kyowa Hakko Kirin, Lilly Japan, Merck Serono, NanoCarrier, Nippon Boeh. M. Kobayashi: Speaker Bureau / Expert testimony: Eisai Inc. H. Kumada: Honoraria (self): AbbVie; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Gilead Sciences; Honoraria (self): MSD; Honoraria (self): Sumitomo; Honoraria (self): Dainippon. S. Kaneko: Honoraria (self): EA Pharma, MSD, Aska Pharma, Astellas Pharma, AbbVie, Eisai, Eidia, Otsuka, Gilead Sciences, Sysmex Corporation, Daiichi Sankyo, Taisho Toyama, Sumitomo Dainippon, Taiho, Takeda, Chugai, Bayer, Bristol-Myers, Mylan EPD, Miyarisan, Mochida, Kowa, Mitsubis; Research grant / Funding (self): Gilead Sciences, AbbVie, Daiichi Sankyo, Astellas Pharma, Takeda, Nippon Boehringer Ingelheim, MSD, Ono Pharma, Pfizer, Shionogi, Teijin Pharma, Mitsubishi Tanabe, Zeria, Abbott Vascular Japan, Taisho Toyama, Novartis, Terumo Corporation, Taiho, Novo Nord. K. Mamontov: Honoraria (self): Bayer; Honoraria (self): Eisai; Honoraria (self): Merck; Honoraria (self): MSD; Honoraria (self): Medtronic; Honoraria (self): Roche. T. Meyer: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Bayer; Advisory / Consultancy: Eisai; Advisory / Consultancy: BTG; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BeiGene; Advisory / Consultancy: Tarveda; Advisory / Consultancy: MSD. K. Mody: Full / Part-time employment: Eisai Inc. T. Kubota: Full / Part-time employment: Eisai Co., Ltd. K. Saito: Full / Part-time employment: Eisai Inc. A.B. Siegel: Full / Part-time employment: Merck. L. Dubrovsky: Full / Part-time employment: Merck. A.X. Zhu: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Eisai; Advisory / Consultancy: Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Sanofi. All other authors have declared no conflicts of interest.
Resources from the same session
2078 - Comprehensive genomic profiling and clinical outcomes in patients (pts) with fibroblast growth factor receptor rearrangement-positive (FGFR2+) cholangiocarcinoma (CCA) treated with pemigatinib in the fight-202 trial
Presenter: Antoine Hollebecque
Session: Poster Display session 2
Resources:
Abstract
3879 - Efficacy of derazantinib (DZB) in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) expressing FGFR2-fusion or FGFR2 mutations/amplifications
Presenter: Michele Droz Dit Busset
Session: Poster Display session 2
Resources:
Abstract
4679 - It’s Not Only About Weight Loss: Tackling Pancreatic Cancer-Associated Cachexia
Presenter: Ana Leonor Matos
Session: Poster Display session 2
Resources:
Abstract
2276 - Frequency and clinicopathological characteristics of biliary tract carcinomas harboring the FGFR2-fusion gene: a prospective observational study (PRELUDE study)
Presenter: Masafumi Ikeda
Session: Poster Display session 2
Resources:
Abstract
2773 - Post-hoc analyses of a subgroup of patients with advanced biliary tract cancer (BTC) who crossed over to treatment with etoposide toniribate (EDO-S7.1) in a randomized Phase II study
Presenter: Ulrich-Frank Pape
Session: Poster Display session 2
Resources:
Abstract
4479 - Capecitabine +Best supportive care (BSC) or Erlotinib +BSC has Overall survival (OS) benefit over BSC alone in unresectable/metastatic Gall bladder cancer(GBC) patients with ECOG PS-III. Results from a phase II Randomised controlled trial (RCT)
Presenter: Babita Kataria
Session: Poster Display session 2
Resources:
Abstract
4843 - FGFR2 fusions and its effect of patient (pt) outcomes in intrahepatic cholangiocarcinoma (iCCA)
Presenter: Daniel Almquist
Session: Poster Display session 2
Resources:
Abstract
2324 - The Clinical Outcomes of Systemic Chemotherapy in Patients with Unresectable or Metastatic Combined Hepatocellular-cholangiocarcinoma (HCC-CCA): Retrospective Study of 120 Patients
Presenter: Eojin Kim
Session: Poster Display session 2
Resources:
Abstract
3678 - High PD-L1 expression is associated with treatment response to pembrolizumab in patients with advanced biliary tract cancer.
Presenter: Gilhyang Kim
Session: Poster Display session 2
Resources:
Abstract
3901 - Genomic profiling in Chinese biliary tract cancer patients with PI3K/AKT/mTOR pathway and RAS gene mutations
Presenter: Jingyu Cao
Session: Poster Display session 2
Resources:
Abstract