Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study
- Study type
- Clinical trial
- Study name
- FIGHT-202
- Phase
- Phase 2
- Design
- Multicentre, open-label, single-arm, multicohort trial at 146 academic or community sites in the USA, Europe, the Middle East and Asia
- Sample size
- 146 patients (107 with FGFR2 fusions or rearrangements); 147 patients in the final analysis
- Source
- Lancet Oncol · 2020
- Trial registration
- NCT02924376
In plain words
People with advanced bile duct cancer (cholangiocarcinoma) whose disease had grown after at least one treatment took pemigatinib tablets. In those whose tumour had a change in the FGFR2 gene, the tumour shrank in about 1 in 3 patients and the disease was controlled for at least some time in most of them; in patients without this change, tumours did not shrink. The most common side effect was a rise in blood phosphate.
Key results
Treatment arms and regimens
Oral pemigatinib at a starting dose of 13.5 mg once daily in 21-day cycles (2 weeks on, 1 week off) until disease progression, unacceptable toxicity, withdrawal of consent or physician decision.
Source of the regimen details: Full text of the Lancet Oncol 2020 paper (PMC8461541) and the FDA label for Pemazyre
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients aged 18 or older with histologically or cytologically confirmed locally advanced or metastatic cholangiocarcinoma, with progression after at least one previous systemic therapy (previous selective FGFR inhibitors were not allowed), measurable disease by RECIST 1.1, ECOG 0 to 2 and life expectancy of at least 12 weeks. Patients were assigned to three cohorts: FGFR2 fusions or rearrangements, other FGF/FGFR alterations, and no FGF/FGFR alterations.
Endpoints
Primary endpoint: proportion of patients with an objective response in the FGFR2 fusion or rearrangement cohort, by independent central review. Secondary endpoints: objective response in the other cohorts, duration of response, disease control, progression-free survival, overall survival, safety and population pharmacokinetics.
Safety and side effects
Hyperphosphataemia was the most common all-grade adverse event (88 of 146, 60%); it started early (median 15 days) and was managed with a low-phosphate diet, phosphate binders (18%), and dose reduction or interruption. 93 patients (64%) had grade 3 or worse adverse events; the most frequent were hypophosphataemia (12%), arthralgia (6%), stomatitis (5%), hyponatraemia (5%), abdominal pain (5%) and fatigue (5%). Serious adverse events occurred in 65 patients (45%), most often abdominal pain (5%), pyrexia (5%), cholangitis (3%) and pleural effusion (3%). Nail toxicity occurred in 42% (grade 3 or worse 2%) and serous retinal detachment in 4%. 9% stopped treatment because of adverse events, and no deaths were deemed treatment related.
Clinical significance and place in guidelines
FIGHT-202 was the basis of FDA accelerated approval of pemigatinib for previously treated cholangiocarcinoma with an FGFR2 fusion or rearrangement, and pemigatinib became the first FGFR inhibitor approved in this disease. ESMO 2025 recommends it after one or more lines of therapy [III, A; ESCAT I-B]. In FIGHT-302 (first line; JCO 2026), pemigatinib improved progression-free survival compared with gemcitabine–cisplatin, but overall survival was similar.
Limitations
A single-arm trial without a comparison group, and overall survival was immature at the first report. Activity was seen only in the FGFR2 cohort, and a validated molecular test is needed to detect this change. The confirmatory phase 3 trial (FIGHT-302) closed early.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.