3879 - Efficacy of derazantinib (DZB) in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) expressing FGFR2-fusion or FGFR2 mutations/amplifications

Background

FGFR2 gene aberrations (GA) include fusions and mutations/amplifications, with an estimated prevalence of approximately 15% and 5% in iCCA, respectively. While FGFR2 fusions are acknowledged oncogenic drivers, the oncogenic potential of FGFR2 mutations and amplifications is less well defined, due to ambiguous available preclinical and clinical data. In a non-comparative Phase 2a study (NCT01752920), the potent pan-FGFR inhibitor DZB was administered to iCCA pts expressing either FGFR2-fusion (N = 29), FGFR2 mutations/amplifications (N = 6) or no FGFR gene aberration (N = 9). Here, we present a post-hoc analysis of outcomes of iCCA pts expressing FGFR mutations/amplifications (N = 6) or no FGFR GA (N = 9) as compared to previously reported data of iCCA pts (N = 29) expressing FGFR2 fusions (Mazzaferro et al. 2018 BJC).

Methods

Pts received 300 mg DZB QD PO. Eligibility criteria included a locally confirmed (FISH or NGS) testing of FGFR2 GA (fusions vs mutations/amplifications or no aberrations). Objective responses were determined per RECIST 1.1. Disease control rate (DCR) was defined by the summation of CR, PR and SD, and PFS, calculated from treatment initiation until disease progression or death.

Results

The table shows the efficacy outcomes in the 3 patient groups. Types of drug-related adverse events were similar across groups. No new safety signals were identified.Table:

721P

Conclusions

Anti-tumor efficacy of DZB as measured by DCR and PFS in iCCA patients harboring an FGFR2 GA seems to be similar for patients with FGFR2 fusions and FGFR2 mutations/amplifications, while patients without any detectable FGFR GA appear to derive no benefit from DZB treatment. While the influence of prognostic variables still has to be confirmed, the anti-tumor efficacy of DZB seen in pts with FGFR2 GA other than fusions warrant further clinical investigation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Basilea Pharmaceutica International Ltd.

Funding

Basilea Pharmaceutica International Ltd.

Disclosure

S. Braun: Full / Part-time employment: Basilea Pharmaceutica Int. Ltd.; Shareholder / Stockholder / Stock options: Ipsen. B. El-Rayes: Advisory / Consultancy: Merrimack; Advisory / Consultancy: BTG; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Loxo; Honoraria (self), Advisory / Consultancy: RTI Health Solutions; Honoraria (self), Speaker Bureau / Expert testimony: Lexicon; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Cleave Biosciences; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): AVEO; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Hoosier Cancer Research Network; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): PPD; Research grant / Funding (institution): Merck; Research grant / Funding (institution): ICON Clinical Research. W.P. Harris: Advisory / Consultancy: Neo Therma; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): ArQule; Research grant / Funding (institution): Halozyme; Research grant / Funding (institution): Nordion; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Agios. N. Damjanov: Advisory / Consultancy: Bayer; Advisory / Consultancy: Amgen; Advisory / Consultancy: Celgene; Honoraria (self): Sirtex Medical. L. Rimassa: Advisory / Consultancy: Bayer; Advisory / Consultancy: Sirtex Medical; Advisory / Consultancy: Italfarmaco; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: ArQule; Advisory / Consultancy: Baxter; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Amgen; Advisory / Consultancy: Incyte; Advisory / Consultancy: Celgene; Advisory / Consultancy: Eisai; Advisory / Consultancy: Lilly; Honoraria (self): AstraZeneca; Honoraria (self): AbbVie; Honoraria (self): Gilead Sciences; Honoraria (self): Roche. F. Braiteh: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Clovis Oncology; Shareholder / Stockholder / Stock options: Agios; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Insys Therapeutics; Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Tesaro; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Genentech/Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Regeneron; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lexicon; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Taiho Pharmaceutical; Travel / Accommodation / Expenses: Heron. S. Lonardi: Advisory / Consultancy, Research grant / Funding (self): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Merck Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Servier. M. Engelhardt: Full / Part-time employment: Basilea Pharmaceutica Int. Ltd. M. Saulay: Full / Part-time employment: Basilea Pharmaceutica Int. Ltd. B. Schwartz: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: ArQule; Advisory / Consultancy: CIRM. W.L. Shaib: Research grant / Funding (institution): ArQule; Research grant / Funding (institution): Lilly. V. Mazzaferro: Advisory / Consultancy: Terumo Europe NV; Speaker Bureau / Expert testimony: Ipsen AB. K.P. Papadopoulos: Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): ArQule; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): ARMO BioSciences; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Calithera Biosciences; Research grant / Funding (institution): Curegenix; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Peloton Therapeutics; Research grant / Funding (institution): ADC Therapeutics; Research grant / Funding (institution): 3D Medicines; Research grant / Funding (institution): Formation Biologics; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Syros Pharmaceuticals; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): OncoMed. All other authors have declared no conflicts of interest.