Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma

Daniel V T Catenacci, Drew Rasco, Jeeyun Lee, Sun Young Rha, Keun-Wook Lee, Yung Jue Bang, Johanna Bendell, Peter Enzinger, Neyssa Marina, Hong Xiang, Wei Deng, Janine Powers, Zev A Wainberg, Daniel V T Catenacci, Drew Rasco, Jeeyun Lee, Sun Young Rha, Keun-Wook Lee, Yung Jue Bang, Johanna Bendell, Peter Enzinger, Neyssa Marina, Hong Xiang, Wei Deng, Janine Powers, Zev A Wainberg

Abstract

Purpose: To evaluate the safety, pharmacokinetics, and preliminary activity of bemarituzumab in patients with FGFR2b-overexpressing gastric and gastroesophageal junction adenocarcinoma (GEA).

Patients and methods: FPA144-001 was a phase I, open-label, multicenter trial consisting of the following 3 parts: part 1a involved dose escalation in patients with recurrent solid tumors at doses ranging from 0.3 to 15 mg/kg; part 1b involved dose escalation in patients with advanced-stage GEA; and part 2 involved dose expansion in patients with advanced-stage GEA that overexpressed FGFR2b at various levels (4 cohorts; high, medium, low, and no FGFR2b overexpression) and 1 cohort of patients with FGFR2b-overexpressing advanced-stage bladder cancer.

Results: Seventy-nine patients were enrolled; 19 were enrolled in part 1a, 8 in part 1b, and 52 in part 2. No dose-limiting toxicities were reported, and the recommended dose was identified as 15 mg/kg every 2 weeks based on safety, tolerability, pharmacokinetic parameters, and clinical activity. The most frequent treatment-related adverse events (TRAEs) were fatigue (17.7%), nausea (11.4%), and dry eye (10.1%). Grade 3 TRAEs included nausea (2 patients) and anemia, neutropenia, increased AST, increased alkaline phosphatase, vomiting, and an infusion reaction (1 patient each). Three (10.7%) of 28 patients assigned to a cohort receiving a dose of ≥ 10 mg/kg every 2 weeks for ≥ 70 days reported reversible grade 2 corneal TRAEs. No TRAEs of grade ≥ 4 were reported. Five (17.9%; 95% CI, 6.1% to 36.9%) of 28 patients with high FGFR2b-overexpressing GEA had a confirmed partial response.

Conclusion: Overall, bemarituzumab seems to be well tolerated and demonstrated single-agent activity as late-line therapy in patients with advanced-stage GEA. Bemarituzumab is currently being evaluated in combination with chemotherapy in a phase III trial as front-line therapy for patients with high FGFR2b-overexpressing advanced-stage GEA.

Trial registration: ClinicalTrials.gov NCT02318329.

Figures

FIG 1.
FIG 1.
Study design. IHC, immunohistochemistry; PK, pharmacokinetics; RD, recommended dose.
FIG 2.
FIG 2.
Mean (± standard deviation) bemarituzumab serum concentration versus time profiles after first dose (cycle 1, day 1). GEA, gastroesophageal adenocarcinoma; P1a, part 1a; P1b, part 1b; P2, part 2.
FIG 3.
FIG 3.
Objective response and duration of follow-up in FGFR2b-positive gastric cancer.
FIG 4.
FIG 4.
Waterfall plot of best percent change in sum of diameters from baseline in FGFR2b-positive gastric cancer. FPA144, bemarituzumab.

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