1241P Phase Ib study of futibatinib plus pembrolizumab in patients with advanced or metastatic solid tumors: Tolerability results and antitumor activity in esophageal carcinoma

Abstract

Combination therapy using FGFR inhibitors and Immune checkpoint inhibitors (ICIs) are being explored as a novel strategy for cancer patients (pts). Here, we report the safety and tolerability of FGFR inhibitor futibatinib plus pembrolizumab in pts with advanced (adv) or metastatic solid tumors and first results for preliminary antitumor activity in pts with esophageal carcinoma (EC). This study consists of Feasibility phase (FP) and Expansion phase (EP). In FP, pts with adv or metastatic solid tumors harboring FGF/FGFR abnormalities received futibatinib 20 mg once daily (QD) plus pembrolizumab 200 mg every 3weeks. In EP, pts with ICIs naive (Cohort A) or ICIs refractory (Cohort B) for adv or metastatic EC harboring FGFR mRNA overexpression who have received at least one prior therapy with a fluorouracil and platinum-based drug received futibatinib plus pembrolizumab at the recommended dose (RD) determined in FP. Primary endpoint was dose-limiting toxicity (DLT) in FP and overall response rate (ORR) in EP; Secondary endpoints included treatment-related adverse events (TRAEs) and disease control rate (DCR). As of November 29, 2021, 11 pts in FP, 9 pts (Cohort A) and 10 pts (Cohort B) in EP were enrolled. No DLTs were observed in FP and the RD of futibatinib in combination with pembrolizumab was determined 20 mg QD. Most common TRAEs in FP (N=11; all grade, grade ≥3) were hyperphosphatemia (91%, 27%), nausea (36%, 0%) and diarrhea (27%, 0%). As results of the interim analysis in EP, confirmed partial responses (PRs) were observed in 4 pts with squamous cell carcinoma (sq) in Cohort A; ORR was 44% with DCR of 78%. In Cohort B, confirmed PRs were observed in 2 pts [1 sq pt; 1 adenocarcinoma (adeno) pt]; ORR was 20% with DCR of 60%. Futibatinib plus pembrolizumab showed well-tolerability and manageable safety profile in pts with adv or metastatic solid tumors. Preliminary antitumor activity was observed not only in ICIs naïve but also in ICIs refractory adv or metastatic EC pts regardless of sq and adeno. Enrollment in EP is ongoing including an additional cohort for ICIs naïve 1st line adv EC and ICIs refractory adv NSCLC pts.