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

• Published in: Annals of oncology Vol. 30; p. v365
• Main Authors: Siefker-Radtke, A.O., Lugowska, I., Tupikowski, K., Andric, Z.G., Rezazadeh Kalebasty, A., Curigliano, G., Vaena, D., Vogl, F.D., Currie, G., Abella, S., Kelly, W.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-10-2019
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz249.016

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).
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 <2. Treatment consisted of V monotherapy at 25mg/kg for 2 weeks followed by the combination of V with P 200mg q3w. Paired tumor biopsies were obtained pre V and 14 days post V treatment. Efficacy was assessed by investigators per RECIST 1.1. Primary objectives were safety and activity.
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 1line 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.
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.
NCT03123055.
Rainier Therapeutics, Inc.
Rainier Therapeutics, Inc.
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.