Clinical Summary:

• Design/Population: Phase 3 FIGHT-302 trial randomizing 167 patients with previously untreated, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 rearrangements to pemigatinib or gemcitabine-cisplatin, with crossover permitted following progression.
• Key Outcomes: Pemigatinib significantly improved progression-free survival, increased objective response rates, and more than doubled median duration of response compared with chemotherapy. Overall survival was similar between groups, likely reflecting extensive crossover to FGFR-targeted therapy.
• Clinical Relevance: These findings support pemigatinib as a frontline treatment option for patients with FGFR2-rearranged cholangiocarcinoma and reinforce the importance of comprehensive genomic testing at diagnosis.

Tanios Bekaii-Saab, MD, Mayo Clinic, Phoenix, Arizona, discusses results from the phase 3 FIGHT-302 trial evaluating first-line pemigatinib in patients with FGFR2-rearranged cholangiocarcinoma. The study represents the largest randomized trial conducted in this molecularly defined population and was designed to determine whether targeted FGFR inhibition could outperform standard chemotherapy in the frontline setting.

Pemigatinib significantly improved progression-free survival and produced substantially higher and more durable response rates than gemcitabine-cisplatin, with a disease control rate approaching 90%. These findings add to growing evidence that biomarker-driven therapies should be incorporated earlier in the treatment course and underscore the need for routine next-generation sequencing in patients with cholangiocarcinoma.

Dr Bekaii-Saab presented these results at the 2026 ASCO Annual Meeting in Chicago, Illinois.

Transcript: 

My name is Tanios Bekaii-Saab, I’m a professor and consultant at Mayo Clinic in Arizona, and I’m a GI medical oncologist.

Today I’ll be discussing the results of one of the studies we presented at ASCO 2026, looking at an agent called pemigatinib for unresectable or advanced cholangiocarcinoma with FGFR2 rearrangements. The study is FIGHT-302.

As background, first-line treatment for advanced metastatic cholangiocarcinoma has traditionally been chemotherapy, and more recently chemotherapy plus immunotherapy. Pemigatinib is an FGFR inhibitor that targets FGFR1, FGFR2, and FGFR3, and it is currently approved for previously treated advanced cholangiocarcinoma with FGFR2 rearrangements.

The goal of this study was to bring pemigatinib into the first-line setting and compare it with standard chemotherapy in patients with advanced or metastatic cholangiocarcinoma harboring FGFR2 rearrangements. Although the study closed early, it remains the largest global phase III trial evaluating the efficacy and safety of pemigatinib in the first-line treatment of locally advanced or metastatic cholangiocarcinoma with FGFR2 rearrangements.

The study screened 4,563 patients for FGFR2 rearrangements. Ultimately, 196 patients were eligible for screening, and 167 patients were enrolled and randomized between pemigatinib and standard gemcitabine plus cisplatin.

Patients randomized to chemotherapy had the option to cross over to pemigatinib after confirmed disease progression.

The study also allowed one cycle of gemcitabine and cisplatin prior to randomization. The primary endpoint was progression-free survival.

The study was fairly balanced in terms of demographics and baseline characteristics. Approximately 13% to 15% of patients had received one prior cycle of gemcitabine and cisplatin before randomization, as specified in the protocol.

The study demonstrated that pemigatinib significantly prolonged progression-free survival compared with chemotherapy. Median progression-free survival was 8.34 months with pemigatinib versus 6.8 months with gemcitabine and cisplatin. The hazard ratio was 0.584, a very strong hazard ratio, with a statistically significant P value of .0078. The response rate with pemigatinib was 47% compared with only 15.5% with gemcitabine and cisplatin.

Not only were there more responders, but the median duration of response was longer—14.2 months versus 6.3 months. Disease control rates were close to 90% with pemigatinib compared with approximately 68% with chemotherapy.

Interestingly, among the 42 patients who crossed over to receive pemigatinib after progression on chemotherapy, the response rate was 38%, and the median duration of response was lower than what was observed in the first-line setting. This further emphasizes the importance of using this active therapy earlier in the course of disease.

Overall survival was similar between the 2 arms, largely because of the crossover design and the availability of FGFR inhibitors both through clinical trials and standard practice. Approximately 80% of patients in the chemotherapy arm ultimately received an FGFR inhibitor.

It is worth noting that the 14 patients who did not receive an FGFR inhibitor after progression had a median overall survival of only 11.1 months. I would also note that five patients in the pemigatinib arm ultimately underwent surgical resection, and at the time of study closure all of these patients remained alive. The safety profile was consistent with the known safety profile of pemigatinib. There were no unexpected safety findings.

We also conducted longitudinal next-generation sequencing and ctDNA analyses on available patient samples. These analyses suggested that approximately one-third of patients developed emergent FGFR2 mutations, further emphasizing that FGFR2 is a key driver pathway in this disease.

In conclusion, this large phase III study demonstrated that pemigatinib is effective and safe and should be considered as a treatment option in the first-line setting for patients with locally advanced or metastatic cholangiocarcinoma harboring FGFR2 rearrangements.

It is important to remember that FGFR2 fusions occur almost exclusively in intrahepatic cholangiocarcinoma and are present in approximately 5% of patients. This is a relatively rare molecular subset, but for those patients with FGFR2 rearrangements, pemigatinib should certainly be considered as a treatment option.

The broader implication is that all patients with cholangiocarcinoma should undergo next-generation sequencing early in the course of their disease, ideally at diagnosis or before treatment decisions are made.

We are increasingly seeing targeted therapies move into the first-line setting. HER2-directed therapies are being evaluated in first-line clinical trials. We now have these results for FGFR2 fusions. There are also studies evaluating IDH1 inhibitors in combination with chemotherapy and immunotherapy in the first-line setting.

More and more, as we have seen across many tumor types, biologic and targeted therapies are moving into earlier lines of treatment.

Source: 

Bekaii-Saab TS, Melisi D, Wilmink J, et al. Pemigatinib for untreated unresectable/metastatic cholangiocarcinoma (mCCA) with fibroblast growth factor receptor-2 (FGFR2) rearrangement: Phase 3 FIGHT-302 results. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 4017.