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Poster session 13

59P - Efficacy of derazantinib in intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions, mutations or amplifications

Date

10 Sep 2022

Session

Poster session 13

Topics

Targeted Therapy;  Molecular Oncology

Tumour Site

Hepatobiliary Cancers

Presenters

Mitesh Borad

Citation

Annals of Oncology (2022) 33 (suppl_7): S19-S26. 10.1016/annonc/annonc1036

Authors

M. Borad1, M. Javle2, W.L. Shaib3, K. Mody4, F. Bergamo5, W.P. Harris6, N. Damjanov7, T. Macarulla Mercade8, G. Brandi9, G. Masi10, M. Droz Dit Busset11, A. Boncompagni12, M. Dimova-Dobreva13, M. Engelhardt14, M. Saulay12, T.R. Halfdanarson15, J. Knox16, G.K. Abou-Alfa17, N. Personeni18, V. Mazzaferro19

Author affiliations

  • 1 Oncology Department, Mayo Clinic Cancer Center, 85259 - Scottsdale/US
  • 2 Gastrointestinal Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 3 Hematology And Oncology, Emory University, 30322 - Atlanta/US
  • 4 Hematology And Oncology, Mayo Clinic, 32224 - Jacksonville/US
  • 5 Dipartimento Oncologia 1, IOV - Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 6 Medicine, University of Washington Medical Center, 98195 - Seattle/US
  • 7 Hematology And Oncology, Abramson Cancer Center at the University of Pennsylvania, 19140-5189 - Philadelphia/US
  • 8 Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO)-Cellex Center, 8035 - Barcelona/ES
  • 9 Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria of Bologna, 40138 - Bologna/IT
  • 10 Oncology Medical, AOU Pisana - Stabilimento di Santa Chiara, 56126 - Pisa/IT
  • 11 Hepatopancreatobiliary And Digestive Surgery, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 20133 - Milan/IT
  • 12 Development Department, Basilea Pharmaceutica Ltd., 4005 - Basel/CH
  • 13 Development, Basilea Pharmaceutica Ltd., 4005 - Basel/CH
  • 14 Development Department, Basilea Pharmaceutica AG, 4058 - Basel/CH
  • 15 Medical Oncology Department, Mayo Clinic, 55905 - Rochester/US
  • 16 Oncology Medical, Princess Margaret Cancer Center, Toronto, ON/CA
  • 17 Medicine Department, Memorial Sloan Kettering Evelyn H. Lauder Breast Center, 10065 - New York/US
  • 18 Department Of Oncology And Hematology, Istituto Clinico Humanitas, 20089 - Rozzano/IT
  • 19 Oncology Medical, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano/IT
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Abstract 59P

Background

In patients (pts) with iCCA, FGFR2 fusions (FGFR2F) occur in ∼15%, FGFR2 mutations or amplifications (FGFR2MA) in ∼5%. These pts have limited options after progression after 1L chemotherapy. Pemigatinib and Infigratinib have received accelerated FDA approval for chemorefractory CCA with FGFR2F. Derazantinib is a potent FGFR1-3 kinase inhibitor.

Here, we present data from 143 patients with FGFR2F or FGFR2MA from the phase II study FIDES-01 (NCT03230318).

Methods

Eligible pts with advanced iCCA, ≥1 prior chemotherapy and FGFR2F or FGFR2MA received derazantinib 300 mg QD. FGFR2F were confirmed by FISH, FGFR2MA were identified by NGS. Primary endpoint was objective response rate (ORR) by central radiology review per RECIST v1.1 for pts with FGFR2F and progression-free survival (PFS) for pts with FGFR2MA. Response and safety was assessed in 103 pts with FGFR2F (ITT). In pts with FGFR2MA, safety was assessed in 40 pts (ITT) and response in 31 pts that were evaluable.

Results

143 pts were dosed, median age 59 y, 63% female, 52% had ≥2 prior treatment lines.

At data cutoff (25-Mar-2022), 98% of 103 pts with FGFR2F and 78% of 40 pts with FGFR2MA had discontinued treatment.

In pts with FGFR2F, confirmed ORR was 21.4% (95% CI 13.9, 30.5), DCR 75.7% (95% CI 66.3, 83.6), mPFS 8.0 mo (95% CI 5.5, 8.3) and mOS 17.2 mo (95% CI 12.5, 22.4).

In pts with FGFR2MA, confirmed ORR was 6.5% (95% CI 0.8, 21.4), DCR 58.1% (95% CI 39.1, 75.5), mPFS 8.3 mo (95% CI 1.9, 16.7) and mOS 15.9 mo (95% CI 8.4, NE). Most common adverse drug reactions (any grade / ≥G3) were hyperphosphatemia (37% / 3%), asthenia/fatigue (34% / 5%), nausea (30% / 1%), transaminase elevations (29% / 12%), dry mouth (27% / 0%) and dry eye (23% / 0%). Drug-related nail toxicities (8% / 0%), retinal events (1% / 0%), stomatitis (1% / 0%) and palmar-plantar erythrodysesthesia (PPE) (1% / 0%) were rare.

Conclusions

Derazantinib results in meaningful clinical benefit for pts with FGFR2 genetic aberrations including FGFR2F and FGFR2MA. Derazantinib-related toxicities were limited: PPE, stomatitis, retinal or nail toxicity were infrequent in the study population.

Clinical trial identification

NCT03230318.

Editorial acknowledgement

Legal entity responsible for the study

Basilea Pharmaceutica International Ltd.

Funding

Basilea Pharmaceutica International Ltd.

Disclosure

M. Borad: Financial Interests, Institutional, Other, Research Support: Basilea. M. Javle: Financial Interests, Personal, Advisory Board: QED, Taiho, Merck, Transthera, Incyte, Servier, AstraZeneca; Financial Interests, Personal, Invited Speaker: Oncosil, Incyte; Non-Financial Interests, Principal Investigator: qed, Basilea. W.L. Shaib: Financial Interests, Personal, Other, Consultatory: Ipsen, BMS, Mylan, Blueprint, Lexicon; Financial Interests, Personal, Principal Investigator: Basilea, GSK, Lexicon, Eli Lilly. K. Mody: Financial Interests, Personal, Other, Employment, stock options/ownership: IMV Inc; Financial Interests, Personal, Other, Scientific Advisory Board, Stock options/ownership: CytoDyn. F. Bergamo: Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Other, accomodation, travel for congress: Bayer, Ipsen W.P. Harris: Financial Interests, Personal, Other, Consulting: Zymeworks, Merck, Boston Scientific; Financial Interests, Personal, Advisory Board: Exelixis, AstraZeneca, Eisai, QED; Financial Interests, Personal, Member of the Board of Directors: GI Cancers Alliance; Financial Interests, Personal, Stocks/Shares: Natera; Financial Interests, Institutional, Other, Institutional Research Funding: AstraZeneca, BMS, Bayer, Merck, Zymeworks, Basilea, Boston Scientific, Koo Foundation, Arqule, Sanofi. N. Damjanov: Financial Interests, Personal, Advisory Board: QED, Bayer. T. Macarulla: Financial Interests, Personal, Advisory Board: (SOBI) Swedish Orpahn Biovitrum AB, Ability Pharmaceutical, SL, Aptitude Health, AstraZeneca, Basilea Pharma, Batxer, BioLineRX Ltd, Celgene SLU, Eisai, Ellipse, Erytech Pharma, Genzyme, Got It Consulting SL, Hirslanden/GITZ, Imedex, Incyte, IPSEN Pharma, Janssen, Lab. Menarini, Lilly, Marketing Farmacéutico & Investigación Clínica, S.L, Medimmune, Medscape, Merck, Sharp and Dhome, Monte Verde SA, Novartis, Novocure, Oncomed Pharmaceuticals, Paraxel, Polaris, PPD Development, QED Therapeutics Inc, Roche, Sanofi-Aventis, Servier, Surface Oncolog, VCN Biosciences; Financial Interests, Personal, Expert Testimony: TRANSWORLD EDITOR; Financial Interests, Institutional, Advisory Board: Zymeworks; Financial Interests, Institutional, Research Grant: Abbvie Farmaceútica, Ability Pharmaceuticals, Agios, Amc Medical Research, Amgen, Armo Biosciences, Aslan, AstraZecena, Basilea, Bayer, Beigene, Biolinerx, Blueprint Medicines, Boston Biomedical, Bristol-Myers Squibb (BMS), Cantargia, Celgene, Eisai, Erytech Pharma, F. Hoffmann-la Roche, Fibrogen, Genentech, Hallozyme, Incyte, Ipsen, Lab. Menarini, Lilly, Loxo Oncology, Medimmune, Merck Sharp & Dohme, Merimarck, Millenim, Nelum, Novartis, Novocure, Oncomed Pharmaceuticals, Pfizer, Pharmacyclics, QED Therapeutics, Roche, VCN Biosciences, Zymeworks; Financial Interests, Personal, Research Grant: Biokeralty Research Institute; Non-Financial Interests, Institutional, Research Grant: Immunomedics; Non-Financial Interests, Personal, Member, ASCO: American Society of Clinical Oncology; Non-Financial Interests, Personal, Member, ESMO: Sociedad Europea de Oncología Médica; Non-Financial Interests, Personal, Member, SEOM: Sociedad Española de Oncología Médica”. G. Brandi: Financial Interests, Personal, Other, pre-clinical protocol granted: Incyte, Ipsen; Financial Interests, Institutional, Other, clinical trial: Incyte, MSD, Roche; Non-Financial Interests, Personal, Other, Founder: APIC (Association of Italian Cholangiocarcinoma Patients); Non-Financial Interests, Personal, Other, Founder and past president: GICO; Non-Financial Interests, Personal, Other, Member of the board: Collegium Ramazzini, European Network for the Study of Cholangiocarcinoma (ENS-CCA), CINBO - National Inter-university Consortium for Bio-Oncology, BLOG (Bologna Liver Oncology Group); Non-Financial Interests, Personal, Other, Coextender: PDTA pathway for Hepatocarcinoma of the Policlinico Sant'Orsola. A. Boncompagni: Financial Interests, Personal, Full or part-time Employment: Basilea Pharmaceutica International. M. Dimova-Dobreva: Financial Interests, Personal, Full or part-time Employment: Basilea Pharmaceutica International. M. Engelhardt: Financial Interests, Personal, Full or part-time Employment: Basilea Pharmaceutica International; Financial Interests, Personal, Stocks/Shares: Basilea Pharmaceutica International. M. Saulay: Financial Interests, Personal, Full or part-time Employment: Basilea Pharmaceutica International. T.R. Halfdanarson: Financial Interests, Personal, Advisory Board: TerSera, Lexicon, Terumo, Curium; Financial Interests, Institutional, Other, Research Support: Basilea, Turnstone Biologics, Advanced Accelerator Applications, Thermo Fisher Scientific, Agios; Non-Financial Interests, Institutional, Advisory Board: Ipsen, TM Isotopen Technologien Muenchen, Crinetics, Viewpoint Molecular Targeting, Advanced Accelerator Applications (a Novartis company); Other, Personal, Leadership Role, not remunerated: North Americal Neuroendocrine Tumor Society (NANETS), Secretaty. 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. G.K. Abou-Alfa: Financial Interests, Personal, Advisory Board: Adicet, Alnylam, AstraZeneca, Autem, Beigene, Berry Genomics, Boehringer Ingelheim, Celgene, Cend, CytomX, Eisai, Eli Lilly, Exelixis, Flatiron, Genentech/Roche, Genoscience, Helio, Helsinn, Incyte, Ipsen, Merck, Nerviano, Newbridge, Novartis, QED, Redhill, Rafael, Servier, Silenseed, Sobi, Vector, Yiviva; Financial Interests, Personal, Other, IP License: PCT/US2014/031545 filed on March 24, 2014, and priority application Serial No.: 61/804,907; Filed: March 25, 2013; Financial Interests, Institutional, Research Grant: Arcus, AstraZeneca, BioNtech, BMS, Celgene, Flatiron, Genentech/Roche, Genoscience, Incyte, Polaris, Puma, QED, Silenseed, Yiviva; Non-Financial Interests, Principal Investigator: AstraZeneca, Yiviva, QED. N. Personeni: Financial Interests, Personal, Other, Lecture: Lilly, Sanofi Aventis; Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, Servier; Financial Interests, Institutional, Other, Research Funding: Basilea, Merck Serono, Servier. All other authors have declared no conflicts of interest.

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