Abstract 603TiP
Background
The pan-FGFR tyrosine kinase inhibitor erdafitinib is approved by the US Food and Drug Administration for adults with locally advanced or metastatic urothelial carcinoma and susceptible FGFR3/2 alterations who have progressed during or after ≥ 1 line of platinum-containing chemotherapy. FGFR alterations are potential oncogenic drivers that have been reported in many solid tumours in adult and pediatric pts. Because of limited response to standard of care options in patients failing systemic therapy, there is strong rationale to assess the safety and efficacy of erdafitinib in adolescent and adult pts with advanced solid tumours and FGFR alterations.
Trial design
This phase II open-label study (RAGNAR/42756493CAN2002; NCT04083976) will include pts aged ≥ 12 years with histologically confirmed unresectable locally advanced or metastatic solid tumours (except urothelial) harboring predefined FGFR mutations or fusions. Eligibility screening includes molecular screening for FGFR alterations by central or local next-generation sequencing assays and other clinical criteria. Pts will enroll into either a broad panel cohort (BPC) of target FGFR alterations or an exploratory cohort (EC) for FGFR alterations not meeting BPC criteria. ∼280 pts (BPC, n = 240; EC, n = 40) will be enrolled. The primary efficacy end point is overall response rate (ORR) per Independent Review Committee. Secondary end points include investigator-assessed ORR, duration of response, disease control rate, progression-free survival, overall survival, safety, pharmacokinetics, and health-related quality of life. Safety assessments include adverse events, vital signs, electrocardiograms, physical examinations, laboratory tests, performance status assessment, growth assessments in adolescents, and ophthalmologic examination. Starting in December 2019, pts will be enrolled at ∼158 sites in 15 countries. Results of this study will provide efficacy and safety data for erdafitinib across multiple solid tumours with FGFR alterations and evaluate potential benefit of targeting underlying altered biology of FGFR irrespective of tumour histology in adult and adolescent pts.
Clinical trial identification
NCT04083976.
Editorial acknowledgement
Writing assistance was provided by Sally Hassan, PhD, of Parexel, and was funded by Janssen Global Services, LLC.
Legal entity responsible for the study
Janssen Research & Development, LLC.
Funding
Janssen Research & Development, LLC.
Disclosure
M. Schuler: Advisory/Consultancy: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Roche, Takeda; Honoraria (self): Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre; Research grant/Funding (institution): AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis. J. Tabernero: Honoraria (self), Advisory/Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Part. C. Massard: Advisory/Consultancy: Amgen, Astellas, AstraZenca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion ; Research grant/Funding (institution): AbbVie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boehringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 bio. G. Vasudeva Iyer: Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy, Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Novartis. O. Witt: Full/Part-time employment: DKFZ Germany; Research grant/Funding (institution): BVD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: BMG. T. Doi: Honoraria (institution), Research grant/Funding (institution): Bristol Myers Squibb; Honoraria (self): Astellas; Honoraria (self), Research grant/Funding (institution): AbbVie; Honoraria (self): Ono; Honoraria (self): Onoclys Biopharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Taiho; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Sumitomo Dainippon; Advisory/Consultancy: Rakuten Medical; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Takeda; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Kyowa Hakko Kirin; Research grant/Funding (institution): Iqiva; Research grant/Funding (institution): Pfizer. C. Lu-Emerson: Advisory/Consultancy: Janssen. D. Hargrave: Advisory/Consultancy: Janssen. J. Garcia-Corbacho: Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: Solti; Travel/Accommodation/Expenses: Bristol-Myers Squibb. S. Little: Shareholder/Stockholder/Stock options, Full/Part-time employment: Janssen, Johnson & Johnson. Q. Xia: Full/Part-time employment: SDS Oncology. A. Santiago-Walker: Shareholder/Stockholder/Stock options, Full/Part-time employment: Janssen. C.H. Moy: Full/Part-time employment: Janssen Research & Development LLC. C. Hammond: Shareholder/Stockholder/Stock options, Full/Part-time employment: Janssen Research & Development LLC. Y.Y. Lau: Full/Part-time employment: Janssen Research & Development LLC. H. Sweiti: Full/Part-time employment: Janssen Research & Development LLC. S. Pant: Honoraria (self): Tyme, Inc., Zymeworks, Xencor and 4-D Pharma; Research grant/Funding (institution): Mirati Therapeutics, Inc., Eli Lilly, Red Hill Biopharma Ltd., Xencor, Five Prime Therapeutics, Novartis, Rgenix, Sanofi-Aventis, Arqule, Bristol-Myers Squibb, Onco Response, Sanofi US Services Inc., GlaxoSmith Kline. All other authors have declared no conflicts of interest.