184TiPFIND: A phase II study to evaluate the efficacy of erdafitinib in FGFR-altered squamous NSCLC

Background: Genomic FGFR alterations and their oncogenic driver potential are frequently observed in various cancers. Initial clinical trials with selective FGFR inhibitors showed moderate responses in FGFR amplified squamous NSCLC (sqNSCLC) patients. However, in FGFR mutated or translocated tumor types a response rate of above 30% was observed. Preclinical cell line and patient-derived sqNSCLC xenograft models with FGFR mutations or translocations indicate strong oncogenic activity and potential sensitivity to FGFR inhibitors. Approximately 3% of all sqNSCLC patients harbor somatic alterations within FGFR genes. However, only some of these mutations are shown to be oncogenic drivers in vitro and in vivo experiments or first in man trials. Trial design: Screening for FGFR mutations/translocations will be performed within the national Network of Genomic Medicine in 15 screening centers in Germany. SqNSCLC patients with activating FGFR genetic alterations will be treated in 11 clinical centers in Germany with the selective FGFR1-4 kinase inhibitor erdafitinib. Archival samples, fresh frozen tumor samples and blood for circulating tumor DNA will be collected before treatment and at time of progression. Patients will be treated until disease progression or unacceptable toxicity. The primary objective of the trial is to analyze the efficacy of erdafitinib in sqNSCLC patients with FGFR genetic driver alterations. Patients will be recruited into 3 cohorts: Cohort 1: high confidence activating FGFR translocations (max. 15 patients); Cohort 2: high confidence activating FGFR mutations (max. 15 patients); Cohort 3: low confidence activating FGFR alteration (ca. 20 patients). The study has been currently submitted by authorities and is currently targeted to start recruitment in Q1/2019. Clinical trial identification: EudraCT: 2018-000399-13. Legal entity responsible for the study: University of Cologne. Funding: Janssen. Disclosure: L. Nogova: Honoraria, advisory boards, travel fees: Boehringer Ingelheim, BMS, Celgene, Roche, Pfizer, Janssen, Novartis; Grants to institution: Pfizer, Novartis, BMS, Janssen. A. Hillmer: Honoraria, advisory board: MSD. S. Merkelbach-Bruse: Honoraria, advisory boards: Novartis, Roche. A. Pinto, C. Woempner: Grants to institution: BMS, Pfizer, Novartis, Janssen. R. Riedel: Honoraria, advisory boards: Boehringer Ingelheim, Novartis; Travel fee: Boehringer Ingelheim, Novartis, Lilly; Grants to institution: BMS, Pfizer, Novartis, Janssen. M. Scheffler: Honoraria, advisory boards: Boehringer Ingelheim; Grants to institution: Pfizer, BMS, Novartis, Janssen. S. Michels: Honoraria, Advisory boards: Novartis; Grants to institution: Pfizer, BMS, Novartis, Janssen. P. De Porre, A. Santiago-Walker: Employee: Janssen; Owning stock: J&J. R.N. Fischer: Honoraria: Bristol-Myers Squibb, MSD, Roche, Boehringer Ingelheim, Novartis, AstraZeneca; Grants to institution: Pfizer, BMS, Novartis, Janssen. D.S. Abdulla: Honoraria, advisory boards: Boehringer Ingelheim, Roche, AbbVie; Grants to institution: Pfizer, Novartis, BMS, Janssen. J. Wolf: Advisory boards, Honoraria, travel fees: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly, MSD, Novartis, Pfizer, Roche; Grants to institution: MSD, BMS, Pfizer, Novartis, Janssen. All other authors have declared no conflicts of interest.