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Initial Results of a Phase 2 FOENIX-CCA2 Study of Futibatinib in Intrahepatic CCA with FGFR2 Fusions/Rearrangements

2021 Year in Review: Cholangiocarcinoma — December 17, 2021

Initial results of the phase 2 FOENIX-CCA2 study demonstrated that second-line futibatinib was active and had a manageable safety profile in patients with intrahepatic CCA harboring FGFR2 fusion/rearrangements.

The pivotal phase 2 FOENIX-CCA2 trial (ClinicalTrials.gov Identifier: NCT02052778) evaluated the investigational FGFR1-4 inhibitor futibatinib in patients with intrahepatic cholangiocarcinoma (iCCA) who harbored FGFR2 fusions/rearrangements. Initial efficacy and safety data for this trial were reported at the 2021 American Association for Cancer Research Annual Meeting.

In the FOENIX-CCA2 study, patients with unresectable/metastatic iCCA with an FGFR2 fusion/rearrangement and progressive disease (PD) after ≥1 prior treatments were enrolled. Eligible patients received oral futibatinib 20 mg once daily until PD or intolerability. The primary end point was objective response rate (ORR) per RECIST version 1.1 by independent central review. Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and patient-reported outcomes (PROs). Data cutoff was October 1, 2020.

A total of 103 patients were enrolled in the study. The median age of the study population was 58 years. The majority of the patients were female (56%), had received ≥2 prior treatments (53%), and harbored FGFR2 fusions (78%) or FGFR2 rearrangements (22%). At data cutoff, treatment was ongoing for nearly 30% of patients.

The study met its primary objective, with a confirmed ORR of 41.7% (43 of 103 patients), including 1 complete response and 42 partial responses. The median DOR was 9.7 months. The median time to response was 2.5 months, with 72% of responses maintained for ≥6 months and 14% of responses lasting for ≥12 months. The DCR was 82.5%. The median PFS was 9.0 months. The median OS was 21.7 months, with a 12-month OS rate of 72%. ORR extended to all prespecified patient demographic subgroups tested, including age, gender, baseline Eastern Cooperative Oncology Group performance status, prior systemic treatment, and prior surgical resection. Dosing modifications did not affect futibatinib response, with an ORR of 40.2% achieved in patients who experienced dosing interruptions and 46.8% in those who underwent dose reductions.

Common treatment-related adverse events (TRAEs) included hyperphosphatemia (91%), nail toxicities (47%), alopecia (33%), and dry mouth (30%). Grade ≥3 adverse events occurred in 77% of patients; hyperphosphatemia, which was the most frequent grade 3 TRAE (31%), resolved with dose modifications/interruptions and phosphate binders. Retinal disorders occurred in 8% of patients and were of grade 1/2 severity. TRAEs were managed with dosing interruptions (50%) or dose reductions (54%); 2 patients discontinued treatment because of TRAEs. No treatment-related deaths were reported. In terms of quality of life, PROs were stable through 11.0 months of treatment.

Findings of exploratory biomarker analyses indicated that responses were independent of molecular alterations, with comparable ORRs achieved in patients with FGFR2 fusions (43.8%), other FGFR2 rearrangements (34.8%), FGFR-BICC1 fusions (41.7%), non-FGFR-BICC1 (44.6%) fusions, and the presence of TP53 co-mutations (ORR, 38.5%).

Based on these results, the investigators concluded that the study met its primary objective and that second-line futibatinib treatment was associated with durable objective responses in patients with iCCA who harbored FGFR2 fusion/rearrangements, independent of patient baseline characteristics, molecular alteration, or dosing modifications. Adverse events were consistent with the class of agents and manageable with dosing modifications.

Source: Goyal L, Meric-Bernstam F, Hollebecque A, et al. CT010 - Primary results of phase 2 FOENIX-CCA2: the irreversible FGFR1-4 inhibitor futibatinib in intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/rearrangements. Presented at: 2021 American Association for Cancer Research Annual Virtual Meeting. Abstract CT010.

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