Interim analysis of the fierce-21 phase 2 (P2) study of vofatamab (B-701), a selective inhibitor of FGFR3, as salvage therapy in metastatic urothelial carcinoma (mUC).

person Begona Mellado Hospital Clinic de Barcelona, Barcelona, Spain info_outline Begona Mellado, Daniel E. Castellano, S Pang, Yuksul Urun, Se Hoon Park, Ulka N. Vaishampayan, Sumanta K. Pal, Graeme Currie, Esteban Abella, Florian D. Vogl, Andrea Necchi

Authors person Begona Mellado Hospital Clinic de Barcelona, Barcelona, Spain info_outline Begona Mellado, Daniel E. Castellano, S Pang, Yuksul Urun, Se Hoon Park, Ulka N. Vaishampayan, Sumanta K. Pal, Graeme Currie, Esteban Abella, Florian D. Vogl, Andrea Necchi Organizations Hospital Clinic de Barcelona, Barcelona, Spain, Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain, Linkou Chang Gung Memorial Hospital, Taoyuan City Taiwan, Taoyuan, Taiwan, Ankara University, Ankara, Turkey, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, Wayne State University, Detroit, MI, City of Hope National Medical Center, Duarte, CA, Rainier Therapeutics Inc, San Leandro, CA, Rainier Therapeutics, Inc, San Leandro, CA, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Patients (pts) with mUC with FGFR3 mutations who have failed platinum-based chemotherapy have a poor prognosis. Their response to immune checkpoint inhibitors appears diminished 10% or less compared to WT pts. 20% of mUC pts harbor FGFR3 mutations or fusions (M/F). Vofatamab is a fully human monoclonal antibody against FGFR3 that blocks activation of the wildtype and genetically activated receptor. FIERCE-21 is a Phase 1b/2 study designed to evaluate vofatamab monotherapy (VFM) or in combination with docetaxel (VFD). Methods: The P2 expansion enrolled mUC pts with FGFR3 M/F+ tumor (identified with FoundationONE CDx™), who failed ≥ 1 prior line of chemotherapy (including prior taxane for pts receiving VFM) or recurred ≤ 12 months of (neo)adjuvant chemotherapy. Pts had measurable disease and ECOG ≤ 1. Treatment consisted of vofatamab at 25 mg/kg alone and in combination with docetaxel at 75 mg/m 2 q3w. Efficacy was assessed by investigators (RECIST 1.1). Primary objectives were safety and objective response-rate (ORR). Results: In the P2, 21 pts each received VFM and VFD. 57% of VFD pts had received at least 2, and 71% of VFM at least 3 prior lines of therapy. Best response to prior therapy was PD for 67% of VFD and 38% of VFM. The safety profile is consistent with previously reported data. TEAEs occurring in > 20% of pts were decreased appetite, diarrhea, pyrexia, asthenia, anemia, dyspnea, and fatigue. Most common vofatamab-related TEAEs in > 10% of pts were asthenia, diarrhea, decreased appetite and rash; all were Grade 1 or 2. In VFM, only 1 pt had a grade 3 TEAE and no pt discontinued treatment due to an AE. There were no cases of hyperphosphatemia, ocular or nail toxicity; 1 pt reported grade 2 skin toxicity. For pts receiving VM, median age was 70 yrs, ECOG 1 = 67%, Hgb < 10 g/dL 5%, liver metastases 19%. Responses have been seen in 7 pts to date including those receiving both VFM and VFD. Conclusions: Vofatamab both alone and combined with D in a q3w schedule are well tolerated with a low frequency of grade 3 TEAEs. Both VFM and VFD have demonstrated efficacy in terms of ORR. PFS/OS and DOR data will be presented at 7+ months for VFD and 9+ months for VFM. Clinical trial information: NCT02401542