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

Abstract

4511 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.