FIERCE-22: Clinical activity of vofatamab (V) a FGFR3 selective inhibitor in combination with pembrolizumab (P) in WT metastatic urothelial carcinoma, preliminary analysis.

person Arlene O. Siefker-Radtke The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Arlene O. Siefker-Radtke, Graeme Currie, Esteban Abella, Daniel A. Vaena, Arash Rezazadeh Kalebasty, Giuseppe Curigliano, Krzysztof Tupikowski, Zoran Gojko Andric, Iwona Lugowska, William Kevin Kelly

Authors person Arlene O. Siefker-Radtke The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Arlene O. Siefker-Radtke, Graeme Currie, Esteban Abella, Daniel A. Vaena, Arash Rezazadeh Kalebasty, Giuseppe Curigliano, Krzysztof Tupikowski, Zoran Gojko Andric, Iwona Lugowska, William Kevin Kelly Organizations The University of Texas MD Anderson Cancer Center, Houston, TX, Rainier Therapeutics Inc, San Leandro, CA, Rainier Therapeutics, Inc, San Leandro, CA, University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City, IA, Norton Cancer Institute, Louisville, KY, University of Milano, European Institute of Oncology, Division of Early Drug Development, Milan, Italy, Dolnoslaskie Centrum Onkologii, Dolnoslaskie, Poland, Clinical Hospital Center, Bezanijska Kosa, Belgrade, Serbia, Centrum Onkologii - Instytut im. Marii Sklodowskiej - Curie, Warsaw, Poland, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company 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%. 20% of pts with mUC harbor FGFR3 mutations or fusions (M/F), which may result in 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. This is a Phase 1b/2 study designed to evaluate V monotherapy window followed in combination of V with P(VP) (NCT03123055). Methods: This trial enrolled mUC pts with failure to ≥ 1 prior line of chemotherapy or recurrence ≤ 12 months of (neo)adjuvant chemotherapy, measurable disease and ECOG <2. Treatment consisted of v at 25 mg/kg alone for 2 week monotherapy window followed by combination with P 200 mg q3w.during the V window paired tumor biopsy were obtained. Efficacy was assessed by investigators (RECIST 1.1). Primary objectives were safety and activity [ORR]). Results: 35 pts have received treatment (Ph1b:8, WT:20, M/F+: 7). WT 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 scores of > 1. The safety profile is consistent with previously reported data for P. TEAE occurring in >20% of patients were nausea, anemia, diarrhea and fatigue. Six WT patients (30%) had responses (4 confirmed responses, 1 unconfirmed), and an additional patient with an iRECIST response. Responses occurred at a median of 3.5 months. At 4+ months of follow up, 13(65%) remain on treatment @ a median of 8 cycles (range: 1-13). At 5+ months the median PFS has not been reached. Conclusions: VP combination therapy is well tolerated with an encouraging ORR and prolonged PFS in the WT cohort; greater than one would anticipate from P alone based upon historical data. We will be reporting 9+ month preliminary PFS/OS and updated OOR/DOR data. Clinical trial information: NCT03123055