The Lynx Group
Cholangiocarcinoma News

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 ( 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.

Related Items

Phase 1 Results of Gunagratinib in Patients with Advanced Solid Tumors Harboring FGFR Pathway Alterations
2021 Year in Review: Cholangiocarcinoma
A phase 1/2a, first-in-human clinical study demonstrated that the highly selective, irreversible pan-FGFR inhibitor gunagratinib was safe and well-tolerated in patients with advanced solid tumors, including CCA.
Prognostic Value of FGFR2 Alterations in Patients Receiving Systemic Chemotherapy for Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
A retrospective analysis indicated the prognostic value of FGFR2 fusions/rearrangements in patients with intrahepatic CCA receiving systemic chemotherapy, which warrants additional study.
FGFR2 Fusion and/or Rearrangement Profiling in Chinese Patients with Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
Epidemiologic data assessed the incidence rate of FGFR2 gene fusion or rearrangement in Chinese patients with intrahepatic CCA, including those with heterogeneous FGFR2 partner genes.
A Comprehensive Genomic and Immune Profiling Study of IDH1- and IDH2-Driven Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
A comprehensive genomic and immune characterization of IDH-mutated and wild-type intrahepatic CCA revealed significant differences in genetic alterations.
Characteristics of IDH Mutations in Bile Duct Carcinoma in a Chinese Population
2021 Year in Review: Cholangiocarcinoma
A retrospective analysis in a large Chinese patient cohort with bile duct carcinoma indicated that activating IDH1/2 mutations occurred at a lower rate compared with that previously reported in the global population.
Silmitasertib (CX-4945) plus Gemcitabine and Cisplatin as First-Line Treatment for Patients with Locally Advanced or Metastatic CCA
2021 Year in Review: Cholangiocarcinoma
Preliminary evidence suggests that combination treatment with silmitasertib plus gemcitabine/cisplatin as first-line therapy has promising efficacy and a favorable safety profile in patients with locally advanced or metastatic CCA.
Targeted Therapies in CCA: Assessment of US Oncologist Practice Patterns
2021 Year in Review: Cholangiocarcinoma
Findings from a clinical practice assessment identified gaps in knowledge, competence, and confidence regarding testing and the use of targeted therapies in patients with unresectable CCA, underscoring the important role of education in overcoming these gaps.
First-Line Toripalimab plus Lenvatinib in Combination with GemOx Chemotherapy for Advanced Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
Results of a phase 2 study indicate that toripalimab and lenvatinib in combination with GemOx chemotherapy provide antitumor activity and reasonable tolerability in patients with advanced intrahepatic CCA.
Comparative Landscape of Actionable Somatic Alterations in Advanced CCA from Circulating Tumor and Tissue-Based DNA Profiling
2021 Year in Review: Cholangiocarcinoma
Findings from a retrospective analysis support the use of both tissue and liquid biopsy biomarker testing to guide therapy selection in patients with advanced CCA, particularly when tissue may not be readily available.
Tibsovo (Ivosidenib) FDA Approved for Advanced or Metastatic Cholangiocarcinoma and IDH1 Mutation
By Loretta Fala
2021 Year in Review: Cholangiocarcinoma
Cholangiocarcinoma (CCA) is an aggressive cancer of the bile duct that forms inside the liver (ie, intrahepatic) or outside the liver (ie, extrahepatic, including perihilar and distal tumors). Individuals with colitis or certain liver diseases may have an increased risk for CCA. Although the precise incidence of CCA is unknown, an estimated 8000 new cases of CCA are diagnosed annually in the United States. It is likely, however, that this number is higher, because CCA is difficult to diagnose and may be misclassified at times.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: