Futibatinib Plus Pembrolizumab for Patients With Metastatic Urothelial Carcinoma

A phase 2 study presented at the European Society for Medical Oncology Congress 2024 highlights the “encouraging” antitumor activity from futibatinib plus pembrolizumab for patients with metastatic urothelial carcinoma (UC).

Encouraging results are particularly noted among patients with FGFR3 mutations or FGFR1-4 fusion or rearrangements. For patients with metastatic UC who are platinum-ineligible, treatment options are limited.

Vadim Koshkin, MD, and colleagues designed a global, two-cohort, non-comparative phase 2 trial to assess the first-line combination of futibatinib—a covalent FGFR1-4 inhibitor—plus pembrolizumab in platinum-ineligible patients with metastatic UC with or without FGFR alterations.

Forty-three patients with no prior systemic therapy, measurable disease, and FGFR3 mutations or FGFR1-4 fusion or rearrangements (cohort A; n=17) or without these alterations (cohort B; n=26) received futibatinib (20 mg oral once daily) plus pembrolizumab (200 mg IV every 3 weeks), irrespective of PD-L1 status.

Dr. Koshkin and colleagues noted that 71% of patients in cohort A and 46% in cohort B had a baseline Eastern Cooperative Oncology Group performance score of 1, and 41% and 31%, respectively, had prior perioperative therapy. In cohort A, 53% had FGFR3 mutations, 35% had FGFR3 fusion/rearrangement, one patient had FGFR2 fusion/rearrangement, and one patient had both an FGFR3 mutation and FGFR1 fusion/rearrangement.

The primary endpoint for each cohort was confirmed objective response rate (ORR) and secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

After a median follow-up of 16.2 months for cohort A and 24.6 months for cohort B, the confirmed ORR was 47% and 31%, respectively. Median PFS was 8.3 months and 4.8 months, respectively, and 12-month OS was 62% and 57%, respectively.

The combination treatment was also well-tolerated; the most commonly reported treatment-related adverse events included hyperphosphatemia (54% of all patients), diarrhea (44%), and dry mouth (37%). This toxicity data was consistent with the known safety profiles of futibatinib and pembrolizumab, with no new safety concerns, researchers added.

“Futibatinib plus pembrolizumab had encouraging antitumor activity with durable responses in patients with metastatic UC, particularly among pts with FGFR3 mutations or FGFR1–4 fusion/rearrangement,” the researchers concluded.