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Developmental therapeutics

1445 - Phase 1 safety and clinical activity of BLU-554 in advanced hepatocellular carcinoma (HCC)


10 Sep 2017


Developmental therapeutics


Clinical Research;  Hepatobiliary Cancers


Richard Kim


Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367


R. Kim1, D. Sarker2, T. Macarulla3, T. Yau4, S.P. Choo5, T. Meyer6, A. Hollebecque7, J. Whisenant8, M. Sung9, J. Yoon10, H.Y. Lim11, A. Zhu12, J. Park13, S. Faivre14, V. Mazzaferro15, H. Shi16, O. Schmidt-Kittler16, C. Clifford16, B. Wolf16, Y. Kang17

Author affiliations

  • 1 Gastrointestinal Oncology, Moffitt Cancer Center, 33612 - Tampa/US
  • 2 Early Phase Trials Unit, Guy’s Hospital, London/GB
  • 3 Medical Oncology, Vall d’Hebron, Barcelona/ES
  • 4 Department Of Medicine, Queen Mary Hospital, Hong Kong/HK
  • 5 Medical Oncology, National Cancer Center, Singapore/SG
  • 6 Ucl Cancer Institute, Oncology, London/GB
  • 7 Oncology, Institut Gustave Roussy, Villejuif/FR
  • 8 Internal Medicine, Huntsman Cancer Institute, Salt Lake City/US
  • 9 Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York/US
  • 10 Seoul National University Hospital, Oncology, Seoul/KR
  • 11 Department Of Medicine, Divisions Of Hematology-oncology, Samsung Medical Center, Seoul/KR
  • 12 Harvard Medical School, Massachusetts General Hospital Cancer Center, Boston/US
  • 13 Center For Liver Cancer, National Cancer Center, Goyang/KR
  • 14 Oncology, Beaujon University Hospital, Clichy/FR
  • 15 Departments Of Surgery, Liver Transplantation And Gastroenterology, Fondazione Istituto Nazionale Tumori (National Cancer Institute) IRCCS, Milan/IT
  • 16 Clinical Development, Blueprint Medicines Corporation, Cambridge/US
  • 17 Oncology, Asan Medical Center , 138-736 - Seoul/KR


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Abstract 1445


Treatment for advanced HCC remains limited and outcomes are poor. However, emerging data implicate FGF19 as a key HCC driver and suggest its receptor, FGFR4 as a novel therapeutic target. A phase 1 study (NCT02508467) was initiated to assess the safety and clinical activity of BLU-554, a potent, highly-selective oral FGFR4 inhibitor.


Adult patients (pts) with advanced HCC and well-preserved liver function received BLU-554 once daily on a 4-week cycle following a 3 + 3 escalation/MTD expansion design. Adverse events (AEs) per CTCAE, PK, PD and pathway activation (tumor FGF19 IHC) were assessed. Response was determined by RECIST 1.1 every 8 weeks.


At a 4/20/17 cutoff, 61 pts have been treated with BLU-554 including 25 in dose escalation (140-900 mg) and 36 in the ongoing dose expansion. 48 (79%) pts had metastatic disease, 54 (89%) had failed ≥1 prior systemic therapy (48 (79%) sorafenib; 11 (18%) nivolumab) and 29 (48%) had pathway activation (IHC+). Based on safety profile, PK, PD, and anti-tumor activity, 600 mg was the MTD and RP2D. Radiographic tumor reduction and objective response per RECIST 1.1 were observed in IHC+ pts in dose escalation and dose expansion. Of 19 IHC+ pts with ≥ 1 radiographic assessment, 11 (58%) pts had tumor reduction: 6 with SD, 4 with PR and 1 with CR (ORR 26%). 6 (32%) IHC+ pts had duration of treatment ≥ 6 months. In contrast, only 4 (15%) of 27 IHC negative pts had tumor reduction (all SD) and only 1 (4%) had duration of treatment ≥ 6 months. Most AEs (regardless of causality) were Grade (Gr) 1-2, including diarrhea (66%), nausea (43%), vomiting (39%), ALT increase (33%), fatigue, AST increase (29% each), abdominal pain (23%), anemia, and decreased appetite (20% each). AST (13%) and ALT (10%) increase, were the only BLU-554-related Gr 3-4 AEs occurring in ≥ 10% of pts. 2 pts experienced DLT (1 Gr 3 abdominal pain; 1 Gr 3 fatigue lasting > 7 days) at 900 mg. 36 (59%) pts have discontinued treatment: 26 disease progression; 5 AE; 3 investigator’s decision; 2 withdrew consent.


BLU-554 is well tolerated at the recommended dose of 600 mg and demonstrates important clinical activity in FGF19 IHC+ advanced HCC pts who have failed prior systemic therapy.

Clinical trial identification


Legal entity responsible for the study

Blueprint Medicines Corporation


Blueprint Medicines Corporation


D. Sarker: Honoraria: Pfizer, Novartis, Bayer, Ipsen. Advisory board: Blueprint, Baxalta. S.P. Choo: Advisory board +/- honoraria: Norvatis; Celgene; Sirtex, Bristol-Myers Squibb; New Beta-Innovation Oncology; Bio-Cancer Treatment; Research grant: Bristol-Myers Squibb, Sirtex. T. Meyer: Advisory board for Merck, Bristol-Myers Squibb, Bayer and Eisai. Grants from Bayer and BTG. J-H. Yoon: Research grants from Bayer HealthCare Pharmaceuticals, Daewoong Pharmaceuticals, and Bukwang Pharmaceuticals. J-W. Park: Honoraria Support from: Bayer, Merck. Advisory Board of: Bristol-Myers Squibb, Merck. Consulting of: Bristol-Myers Squibb, ONO, Bayer. S. Faivre: Consulting of Bayer, BMS, Lilly, Merck Serono, Novartis. Y-K. Kang: Advisory Board of Blueprint, Novartis, Roche, Merck, Ono, Bristol-Myers Squibb, LSK Biopharma, Daehwa, Taiho. All other authors have declared no conflicts of interest.

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