Presentation Authors: Andrea Necchi*, Milan, Italy, Daniel Castellano, Madrid, Spain, Begona Mellado, Barcelona, Spain, See Tong Pang, Taoyuan, Taiwan, Urun Yuksel, Ankara, Turkey, Se Hoon Park, Seoul, Korea, Republic of, Ulka Vaishampayan, Detroit, MI, Graeme Currie, Steve Abella, San Ramon, CA, Sumanta Pal, Los Angeles, CA
Introduction: Patients (pts) with mUC who have failed platinum-based chemotherapy have a poor prognosis. About 20% of them usually respond to immune checkpoint inhibitors (ICI). Also, 20% of pts with mUC harbor FGFR3 mutations or fusions (M/F), and this feature may be associated with lower sensitivity to ICI. Vofatamab (B-701) 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 (VM) or in combination with docetaxel (VD).
Methods: The study consists of a Phase 1b lead-in (P1b with VD), previously reported followed by Phase 2 (P2) expansion cohort in FGFR3 M/F+ pts (identified with the FoundationONE CDxâ„¢ assay on archival samples). The study enrolled mUC pts with failure to â‰¥ 1 line prior chemotherapy (including prior taxane treatment) or â‰¤12 months of (neo)adjuvant chemotherapy, measurable disease and ECOG â‰¤ 1. Treatment consisted of vofatamab at 25 mg/kg alone (VM) and in combination with D (VD) at 75 mg/m2 q3w. Efficacy was assessed by investigators (RECIST 1.1). Primary objectives were safety and activity (objective response-rate [ORR]).
Results: 55 pts have received treatment. In the Ph 2 study, 21 pts received VM, 15 pts received VD. 35% of pts were included as 2nd line therapy, 65% in 3rd or later line of treatment. For pts receiving VD, safety was consistent with Ph 1B data. For pts receiving VM, median age was 70 yrs, ECOG 1 = 67%, Hgb < 10 gm/dL 5%, liver metastases 19%, â‰¥ 2 prior regimens 53%, (best response to prior therapy PD 29%). TEAEs occurring in â‰¥5% patients were asthenia (19%), diarrhea (9.5%), flushing (14%), chills (9.5%), hypotension (9.5%), decreased appetite (19%) and creatinine increased (9.5%). The majority of TEAS were grade 1 and 2. Only 1 patient on MF had a grade 3 TEAE and only 1 patient discontinued treatment due to an AE. Responses have been seen in 7 pts to date including those receiving both VM and VD.
Conclusions: Vofatamab both alone and combined with D in an every 3-week schedule are well tolerated with a low frequency of grade 3 TEAEs. Both VM and VD have demonstrated efficacy in terms of ORR, and mature results with PFS data will be presented.
Source of Funding: BioClin Therapeutics, Inc