Abstract 73P
Background
Biliary tract cancer (BTC) is a rare, heterogenous, and lethal group of cancers with limited treatment options. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Prior analysis of this phase I study found an objective response rate of 23.3% and a manageable safety profile in patients with pretreated BTC who received bintrafusp alfa 1200 mg. We present long-term follow-up safety and efficacy data for bintrafusp alfa in patients with pretreated BTC.
Methods
In this expansion cohort of an ongoing phase I, open-label trial (NCT02699515), Asian patients with BTC for which first-line (1L) chemotherapy failed received bintrafusp alfa 1200 mg Q2W until confirmed disease progression, unacceptable toxicity, or withdrawal. The primary objective was safety/tolerability; secondary objectives included investigator-assessed best overall response per RECIST 1.1.
Results
As of 24 October 2019, 30 patients with pretreated BTC received bintrafusp alfa for a median duration of 8.9 (range, 2-140.1) weeks; median follow-up was 122 weeks, 8 patients were still alive and 3 remained on treatment. The overall safety profile remained consistent with the prior analysis; with no additional deaths or safety signals, and 2 new grade ≥3 TRAEs (grade 3 rash and grade 3 keratoacanthoma). The median overall survival (OS) was 12.7 months [95% CI, [6.7-15.8]; the 12- and 24-month OS rates were 52.0% and 27.7%, respectively. The median duration of response was 18 (range, 2.8-24+) months, with 3 ongoing responses (18+, 23.5+, and 24+ months) of 7 responders (42.8%); the proportion of ongoing responses at 12 and 18 months was 57.1% and 42.8%, respectively.
Conclusions
After 28 months, bintrafusp alfa continues to demonstrate manageable safety with durable responses and long-term survival in Asian patients with pretreated BTC. Bintrafusp alfa is under further investigation as a 1L (NCT04066491) and 2L (NCT03833661) treatment option for patients with locally advanced/metastatic BTC.
Clinical trial identification
NCT02699515.
Editorial acknowledgement
Medical writing support was provided by Spencer Hughes, PhD, of ClinicalThinking, Inc, Hamilton, NJ, USA, and funded by Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline.
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany.
Funding
Merck KGaA, Darmstadt, Germany and GlaxoSmithKline.
Disclosure
C. Yoo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Servier; Honoraria (self): Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Ono Pharmaceuticals. D-Y. Oh: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Bayer; Advisory/Consultancy: Taiho; Advisory/Consultancy: ASLAN; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Zymeworks; Advisory/Consultancy: Celgene; Research grant/Funding (self): Array; Research grant/Funding (self): Eli Lilly. H.J. Choi: Advisory/Consultancy: Bayer; Advisory/Consultancy: ONO; Advisory/Consultancy: MSD. M. Kudo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self): Bayer; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): Lilly; Honoraria (self), Research grant/Funding (institution): EA Pharma; Advisory/Consultancy: Ono; Advisory/Consultancy: Roche; Research grant/Funding (institution): Gilead Sciences; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Sumitomo Dainippon Pharma; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Otsuka; Research grant/Funding (institution): Abbvie. M. Ueno: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Yakult Honsha; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Merck Biopharma; Honoraria (self), Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Dainippon Sumitomo Pharma; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Astellas. S. Kondo: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Abbie; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): AZD; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Boehringer Ingelheim. L-T. Chen: Honoraria (self): ONO; Honoraria (self): Eli Lilly; Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy: PharmaEngine; Honoraria (self), Research grant/Funding (institution): TTY; Honoraria (self), Research grant/Funding (institution): SyncorePharm; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Leadership role: National Institute of Cancer Research, Taiwan; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Polaris; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): BMS; Licensing/Royalties, ENO-1 mAb: HuniLife; Full/Part-time employment: National Health Research Institutes, Taiwan; Officer/Board of Directors: SinoPharm Taiwan, Ltd. M. Osada: Full/Part-time employment: Merck Biopharma. C. Helwig: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck KGaA. I. Dussault: Full/Part-time employment: EMD Serono. M. Ikeda: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self): Taiho; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self): Teijin; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Astrazeneca; Research grant/Funding (institution): Ono; Research grant/Funding (institution): Bristol Myers; Research grant/Funding (institution): MSD; Research grant/Funding (self): J-Pharma; Research grant/Funding (institution): ASLAN; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Astellas.