Lirafugratinib, an innovative treatment targeting FGFR2 mutations, has demonstrated notable antitumor activity in patients with advanced cholangiocarcinoma (CCA) as reported in the ReFocus trial. This phase 1/2 clinical trial showcased the potential of lirafugratinib in a population previously subjected to standard therapies.
Study Overview and Patient Cohorts
In the ReFocus trial, participants received a daily dosage of 70 mg lirafugratinib. The study particularly focused on patients with unresectable or metastatic CCA harboring FGFR2 fusions or rearrangements. The results were presented at the 2026 ASCO Gastrointestinal Cancers Symposium, highlighting the drug’s efficacy in a challenging patient demographic.
The independent review committee evaluated the pivotal cohort, which included 114 patients who had been pretreated with chemotherapy but were naive to FGFR inhibitors. The analysis reported an impressive objective response rate (ORR) of 46.5%, with 2.6% of patients achieving a complete response (CR) and 43.9% a partial response (PR). Moreover, 50% of patients had stable disease (SD), contributing to a disease control rate (DCR) of 96.5%.
Key Efficacy Metrics
The trial’s efficacy metrics revealed significant findings. The median duration of response (DOR) for the pivotal cohort was 11.8 months, while the median progression-free survival (PFS) reached 11.3 months. Patients also enjoyed a median overall survival (OS) of 22.8 months, showcasing lirafugratinib’s potential to extend life in a challenging cancer landscape.
Additional patient groups exhibited varied results. In group 1A, which included patients pretreated with FGFR inhibitors and chemotherapy, the ORR was 22.6%, while group 6, consisting of chemotherapy-naive patients, showed a remarkable ORR of 63.6%. These findings contribute to a nuanced understanding of how prior treatments may impact responses to lirafugratinib.
Treatment Duration and Safety Profile
The median duration of treatment with lirafugratinib was analyzed across different cohorts. Patients in the pivotal cohort received treatment for a median of 41 weeks, while those in groups 1A and 6 had median durations of 27 weeks and 36 weeks, respectively.
Lead author Dr. Antoine Hollebecque from the Gustave Roussy Cancer Institute emphasized the drug’s manageable safety profile, which aligns with FGFR2 inhibition expectations. The most commonly reported adverse effects included stomatitis and palmar-plantar erythrodysesthesia (PPE), both of which were reversible and manageable.
Patient Selection Criteria
The trial enrolled patients aged 18 and older with histologically confirmed unresectable or metastatic CCA, as defined by RECIST v1.1 criteria. Participants were required to be refractory or relapsed from standard therapies, or to have no standard treatment options available. Additionally, patients were selected based on their ECOG performance status and documented FGFR2 genomic alterations.
The study’s design included a dose-escalation phase that evaluated various dosing schedules before establishing the recommended phase 2 dose of 70 mg for daily administration.
Demographics and Treatment History
The pivotal cohort included a median age of 57 years, with a majority being female and Caucasian. Geographically, 41.2% of participants were treated in North America, followed by Europe and the Asia-Pacific region. Most patients had undergone at least one line of prior systemic therapy, with common regimens being gemcitabine-based treatments and fluoropyrimidine-based therapies.
Adverse Events and Safety Monitoring
The safety profile of lirafugratinib was closely monitored, revealing that treatment-related adverse events (TRAEs) were reported in all patients within the pivotal safety population. Notably, grade 3 or higher TRAEs occurred in 57.8% of participants, though none resulted in fatalities. The most frequent TRAEs included nail toxicities, PPE syndrome, and stomatitis, with a significant percentage leading to dose interruptions.
Conclusion
The findings from the ReFocus trial underscore the potential of lirafugratinib as a viable treatment option for patients with FGFR2-mutated advanced cholangiocarcinoma. With a favorable safety profile and promising efficacy metrics, lirafugratinib may represent a significant advancement in the therapeutic landscape for this challenging cancer.
Key Takeaways
- Lirafugratinib shows a 46.5% objective response rate in previously treated advanced cholangiocarcinoma patients with FGFR2 mutations.
- The median duration of response was 11.8 months, indicating prolonged efficacy.
-
Common adverse effects were manageable and reversible, aligning with the expected profile for FGFR2 inhibitors.
-
The trial reinforces the importance of patient selection based on treatment history and genomic profiling in optimizing therapeutic outcomes.
Read more → www.cancernetwork.com