1621P - Efficacy and safety of erdafitinib in adults with pancreatic cancer and prespecified fibroblast growth factor receptor alterations (FGFRalt) in the phase II open-label: Single-arm RAGNAR trial

Background

Erdafitinib (erda) is an oral selective pan-FGFR tyrosine kinase inhibitor approved for treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible FGFR3/2alt who have progressed during or after ≥1 line of platinum-based chemotherapy. Interim results from the RAGNAR study demonstrated tumor agnostic efficacy in patients (pts) with advanced solid tumors with predefined FGFRalt after failure of standard therapies (tx) (Loriot et al, ASCO 2022 ). Here we report results on pts with pancreatic cancer in RAGNAR.

Methods

Pts with advanced or metastatic pancreatic cancer with prespecified FGFR1-4alt (mutations or fusions), disease progression after ≥1 line of systemic tx, and who exhausted standard tx received oral erda until disease progression or intolerable toxicity. Primary end point is objective response rate (ORR) by independent review committee (IRC). Secondary endpoints include duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Results

At data cutoff (median survival f/u 15.24 mo), 18 pts with pancreatic cancer received erda. Median age was 60.5 y (range 34-78); 17 (94.4%) had visceral metastases; median 3 prior lines of systemic tx (range 1-9); 1 (5.6%) responded to last line of tx. All 18-pts had FGFR fusions (14 FGFR2, 4 FGFR1); none had FGFR mutations. None of the pts had KRAS co-alterations. ORR by IRC was 55.6% (95% CI 30.8-78.5). Median time to onset of response was 1.45 mo. Responses were observed in pts with FGFR1 and FGFR2 fusions. Median DCR was 94.4%. Median DOR, PFS and OS were 7.1 mo, 7.0 mo, and 19.7 mo respectively. Investigator-assessed efficacy data were comparable to IRC. The most common adverse events (AEs) were dry mouth (72%), diarrhea (67%), stomatitis (67%), dry skin (67%), hyperphosphatemia (56%), and fatigue (50%); 5 (28%) had serious AEs; 2 (11%) discontinued erda due to AEs. No treatment-related deaths were observed.

Conclusions

Erda demonstrated robust and clinically meaningful activity in pancreatic cancer pts with FGFRalt. Safety data were consistent with erda safety profile.

Clinical trial identification

NCT04083976.

Editorial acknowledgement

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

S. Pant: Financial Interests, Personal, Advisory Role: Zyemworks, Ipsen, Novatris, Janssen; Financial Interests, Institutional, Research Funding: Mirati Therapeutics, Lilly, Xencor, Novartis, Regenix, Bristol Myers Squibb, Astellas Pharma, Purple Biotech, 4D Pharma, Boehringer Ingelheim, NGM Biopharmaceuticals, Janssen, Arcus Biosciences, Elicio Therapeutics. D. Arnold: Financial Interests, Personal, Speaker, Consultant, Advisor: ACE Oncology, Amgen, Art Tempi Media, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, Personal Aptitude Health, Clinical Care Options (COO), CRA International, Eli Lilly, Hexal, IMedex Ipsen, IQVIA, Ketchum, MedAhead, Merck, Merck, Sh; Financial Interests, Personal, Leadership Role: OncoLytics (Project Lead). Maria Alsina. Consultancy/advisory role and honoraria: Amgen, Bristol Myers Squibb, MSD, Lilly, Servier. Markus Moehler. Consultancy/advisory role and honoraria: Amgen, Bristol Myers Squibb, Lilly, MCI Group, Merck, MSD, . J. Tabernero: Financial Interests, Personal, Speaker, Consultant, Advisor, Advisory/Consultancy Fees: Bosch Health Campus (BHC), Karolinska Comprehensive Cancer Centre, Oncode Institute, Oslo University Hospital Comprehensive Cancer Center (OUH CCC),Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiff Oncology, Chugai, Daiichi S; Financial Interests, Personal, Other, Honoraria: Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER); Financial Interests, Personal, Member of Board of Directors: Cancer Core Europe, Horizon Europe Cancer Mission, Spanish Association Against Cancer-AECC; Financial Interests, Personal, Leadership Role: Institute for Health Research INCLIVA Clinical Hospital of Valencia, IdiSNA Universidad de Navarra, Spanish National Cancer Research Center (CNIO), European Organization for Research and Treatment of CancerEORTC, World Innovative Networking (WIN; Financial Interests, Personal, Principal Investigator: Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX Non-financial SAS, Hutchison MediPharma International; Financial Interests, Personal, Other, President: Oncology Master PlanCatalonia Department of Health; Financial Interests, Personal, Other: Oncology Master PlanCatalonia Department of Health (President), Advisory Committee on Pharmaceutical Provision Financing under the Spanish Government (Advisory Committee), Array Biopharma Inc (Coordinating PI & Steering Committee Member, Clini). Y. Loriot: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Immunomedics, Janssen; Financial Interests, Institutional, Speaker, Consultant, Advisor: MSD Oncology; Financial Interests, Personal, Other, Travel reimbursment: Astellas, AstraZeneca, Janssen Oncology, MSD Oncology, and Roche; Financial Interests, Institutional, Research Funding: Astellas Pharma, AstraZeneca, Basilea, Bristol Myers Squibb, Exelixis, Gilead Sciences, Incyte, Janssen Oncology, Merck KGaA, MSD Oncology, Nektar, Pfizer, Roche, Sanofi, and Taiho Pharmaceutical. G.M. Haag: Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, MSD Sharp & Dohme, Lilly, Novartis, Daiichi Sankyo, Servier; Financial Interests, Personal, Other, Honoriaria: Servier, MSD Sharp and Dohme; Financial Interests, Personal, Other, Support for attending Meetings/Travel: Servier, Bristol Myers Squibb, Lilly. D. Palmer: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, AstraZeneca, Eisai, Sirtex Medical, Roche, Boston Scientific, Viatris Research Funding: BMS, Bayer, Sirtex Medical, AstraZeneca, NuCana; Financial Interests, Institutional, Speaker, Consultant, Advisor: Bristol Meyers-Squibb. H. Prenen: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Roche, Bayer, Ipsen, Sanofi. I. Lugowska: Financial Interests, Institutional, Research Grant: Agenus, Roche; Financial Interests, Personal, Writing Engagement: ESMO, Roche; Financial Interests, Personal and Institutional, Coordinating PI: MSD, Roche, BMS, Janssen, Astra, Amgen, RyVu, Incyte, Siropa, Menarini, Celon, Pfizer, Agenus, Rhizen. A. Cervantes: Financial Interests, Institutional, Research Grant: Actuate Therapeutic, Adaptimmune, Affimed Amgen, Astellas Pharma, AstraZeneca, Lilly, MedImmune, Merck, MSD, Natera, Novartis, Ribon Therapeutics Roche, Takeda, Bayer, F. Star Therapeutics, Genentech, Gilead, Janssen; Financial Interests, Personal, Invited Speaker: Amgen, Foundation Medicine, Merck, Roche; Financial Interests, Institutional, Advisory Board: AnHeart Therapeutics GSK Merck Roche Transgene, AbbVie, Amgen; Financial Interests, Personal, Officer, ESMO President: ESMO; Financial Interests, Personal, Other, Associate Editor: ESMO Open, Annals of Oncology; Financial Interests, Personal, Other, Editor In Chief: Cancer Treatment Reviews; Financial Interests, Personal, Advisory Board, Scientific Director: INCLIVA Biomedical Research Institute. M. Gutierrez: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Celularity and Guardant. H. Sweiti, S. Thomas, S. Triantos, L. Crow: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. C. Hammond, S. Najmi: Financial Interests, Personal, Advisory Board, Employment: Janssen. M.H.H. Schuler: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen Oncology, Merck, Novartis, Roche, Sanofi, and Takeda; Financial Interests, Personal, Other, Honoraria: Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen-Cilag, and Novartis; Financial Interests, Institutional, Research Funding: AstraZeneca and Bristol Myers Squibb; Financial Interests, Institutional, Royalties: PCR. All other authors have declared no conflicts of interest.