917PClinical activity of vofatamab (V), an FGFR3 selective antibody in combination with pembrolizumab (P) in metastatic urothelial carcinoma (mUC), updated interim analysis of FIERCE-22

Background Patients (pts) with mUC who have failed platinum-based chemotherapy have a poor prognosis. Reported response rates to immune checkpoint inhibitors (ICI) are approximately 20%. Pts that harbor FGFR3 mutations or fusions (M/F) or have high FGFR3 expression, may have a lower sensitivity to ICI. V (B-701) is a fully human monoclonal antibody against FGFR3 that blocks activation of both the wildtype and genetically activated receptor. FIERCE-22 is a Phase 1b/2 study designed to evaluate V in combination with P (VP). Methods The phase 2 (P2) study enrolled mUC pts who had failed to ≥ 1 prior line of chemotherapy or had recurred within 12 months of (neo)adjuvant chemotherapy. Pts had measurable disease and ECOG Results In the P2, 28 pts have received treatment (wild-type (WT):20, M/F: 8). Patients were unselected for PD-1 status, predominately male (55%) white (95%), all had received at least 1 line of prior chemo and 60% had Bellmunt score of > 1. The safety profile was consistent with previously reported data for P. TEAE occurring in > 20% of patients were anemia, fatigue, pyrexia, and diarrhea. V-related TEAEs reported in > 2 pts were diarrhea, fatigue and pyrexia. The combination was active across M/F and WT tumors as previously reported. At median follow-up time of 7.5 months, the ORR in the tumor response evaluable population is 29.6% and the median PFS is 4.7 months. Nine pts (32%) are continuing study treatment plus 9 pts are in long-term survival follow up. Conclusions VP combination therapy is well tolerated with encouraging ORR and prolonged PFS compared to historical data from P alone. We will present updated safety and efficacy data including OS at 12 months. Clinical trial identification NCT03123055. Legal entity responsible for the study Rainier Therapeutics, Inc. Funding Rainier Therapeutics, Inc. Disclosure A.O. Siefker-Radtke: Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar Therapeutics; Advisory / Consultancy, Travel / Accommodation / Expenses: Seattle Genetics; Advisory / Consultancy: Bavarian Nordic. I. Lugowska: Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Research grant / Funding (self): Merck; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self): Amgen; Honoraria (self): Janssen; Honoraria (self), Research grant / Funding (self): Novartis. A. Rezazadeh Kalebasty: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Exelexis; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Research grant / Funding (institution): Macrogenics; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): Beyond Spring; Research grant / Funding (institution): Rainier Therapeutics; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Bavarian Nordic; Research grant / Funding (institution): Seattle Genetics; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Shareholder / Stockholder / Stock options: ECOM; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi; Honoraria (self), Speaker Bureau / Expert testimony: Amgen; Travel / Accommodation / Expenses: Prometheus labs. G. Curigliano: Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Seagen. F.D. Vogl: Full / Part-time employment: Rainier Therapeutics. G. Currie: Full / Part-time employment, Officer / Board of Directors: Rainier Therapeutics. S. Abella: Full / Part-time employment, Officer / Board of Directors: Rainier Therapeutics. All other authors have declared no conflicts of interest.