FIGHT-302: trial | Bending the Curve: Trial by Trial

FIGHT-302

A Phase 3, Open-Label, Randomized, Active-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Gemcitabine Plus Cisplatin Chemotherapy in First-Line Treatment of Participants With Unresectable or Metastatic Cholangiocarcinoma With FGFR2 Rearrangement (FIGHT-302)

Phase 3N = 167NCT03656536

Population

Adults with histologically or cytologically confirmed, unresectable, locally advanced or metastatic cholangiocarcinoma with a documented FGFR2 rearrangement, receiving first-line treatment (one cycle of gemcitabine-cisplatin before randomisation was allowed).

Design

Open-label, randomised (1:1), active-controlled phase 3 trial of first-line pemigatinib 13.5 mg once daily versus gemcitabine 1,000 mg/m2 plus cisplatin 25 mg/m2 on days 1 and 8 of 3-week cycles (up to 8 cycles), stratified by prior receipt of chemotherapy, geographic region and tumour burden. Crossover to second-line pemigatinib was allowed after progression on chemotherapy. Primary endpoint: progression-free survival by independent central review. Closed early because of a change in standard of care; 4,563 patients were prescreened and 196 screened.

Primary endpoint

PFS

Arms

Gemcitabine plus cisplatin (control, n = 84): Gemcitabine 1,000 mg/m2 plus cisplatin 25 mg/m2 on days 1 and 8 of 3-week cycles, up to 8 cycles
Pemigatinib (experimental, n = 83): Pemigatinib 13.5 mg orally once daily

People

Bekaii-Saab TS

PFSHR 0.58 (95% CI 0.39–0.87)Δ median PFS+1.5 monthsΔ ORR+32 pointsΔ median DOR+7.9 monthsΔ median OS−0.6 months

Show the numbers

Results reported for FIGHT-302
Endpoint	Analysis	Pemigatinib	Gemcitabine plus cisplatin	Effect
PFSITT: all randomised patients (167)	primaryBekaii-Saab 2026	median 8.3 months	median 6.8 months	HR 0.58 (95% CI 0.39–0.87)P=.0078 (nominal)Assessed by independent central review per RECIST v1.1. The paper calls the P value nominal because the trial closed early with a reduced sample size and event count. Median progression-free survival in the crossover group (42 patients given second-line pemigatinib) was 8.1 months.
ORRITT: all randomised patients (167)	primaryBekaii-Saab 2026	47%	15%	Secondary endpoint, assessed by independent central review; the full text gives an odds ratio of 5.57 (95% CI 2.54 to 12.24).
DORResponders in the ITT population	primaryBekaii-Saab 2026	median 14.2 months	median 6.3 months	Secondary endpoint; no confidence intervals are given in the abstract.
OSITT: all randomised patients (167)	primaryBekaii-Saab 2026	median 24.4 months	median 25 months	Described in the abstract as similar between groups; no confidence intervals or hazard ratio in the abstract. Crossover to pemigatinib after progression on chemotherapy was allowed (42 patients crossed over), which confounds the overall survival comparison.

Results reported for FIGHT-302
Endpoint	Analysis	Pemigatinib	Gemcitabine plus cisplatin	Effect
PFSITT: all randomised patients (167)	primaryBekaii-Saab 2026	median 8.3 months	median 6.8 months	HR 0.58 (95% CI 0.39–0.87)P=.0078 (nominal)Assessed by independent central review per RECIST v1.1. The paper calls the P value nominal because the trial closed early with a reduced sample size and event count. Median progression-free survival in the crossover group (42 patients given second-line pemigatinib) was 8.1 months.
ORRITT: all randomised patients (167)	primaryBekaii-Saab 2026	47%	15%	Secondary endpoint, assessed by independent central review; the full text gives an odds ratio of 5.57 (95% CI 2.54 to 12.24).
DORResponders in the ITT population	primaryBekaii-Saab 2026	median 14.2 months	median 6.3 months	Secondary endpoint; no confidence intervals are given in the abstract.
OSITT: all randomised patients (167)	primaryBekaii-Saab 2026	median 24.4 months	median 25 months	Described in the abstract as similar between groups; no confidence intervals or hazard ratio in the abstract. Crossover to pemigatinib after progression on chemotherapy was allowed (42 patients crossed over), which confounds the overall survival comparison.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.58	0.39–0.87

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Pemigatinib (experimental)
Gemcitabine plus cisplatin (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Pemigatinib	Gemcitabine plus cisplatin
0	100.0%	100.0%
5	65.9%	60.1%
10	43.4%	36.1%
16	26.3%	19.6%
21	17.3%	11.8%

Illustrative — modelled from reported values, not trial data. DOR, primary.

Show curves

Pemigatinib (experimental)
Gemcitabine plus cisplatin (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Pemigatinib	Gemcitabine plus cisplatin
0	100.0%	100.0%
9	64.4%	37.1%
18	41.5%	13.8%
27	26.8%	5.1%
36	17.3%	1.9%

Appears in

2024 FGFR2 first-line trials end early; infigratinib approval withdrawn

Sources

Bekaii-Saab TS, Melisi D, Wilmink H, Garufi C, Tran N, Tortora G, et al. Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor-2 Rearrangement: Results From the Phase III FIGHT-302 Trial. J Clin Oncol. 2026;44(23):2187-2197.
PubMed DOI