Pemigatinib in previously treated solid tumors with activating FGFR1-FGFR3 alterations: phase 2 FIGHT-207 basket...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Fibroblast growth factor receptor (FGFR) alterations are key drivers of oncogenesis in various cancers.
• Targeting FGFR signaling represents a promising therapeutic strategy for FGFR-altered tumors.

Purpose of the Study:

• To evaluate the efficacy and safety of pemigatinib, a selective FGFR1-FGFR3 inhibitor, in patients with advanced solid tumors harboring FGFR alterations.
• To explore response rates, survival outcomes, and identify predictive biomarkers and resistance mechanisms.

Main Methods:

• Phase 2, open-label, single-arm, multicenter FIGHT-207 basket study.
• Patients with advanced solid tumors and specific FGFR alterations (fusions/rearrangements, activating non-kinase domain mutations, kinase domain mutations) were enrolled.
• Objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS) were assessed.

Main Results:

• ORRs were 26.5% (cohort A: fusions/rearrangements), 9.4% (cohort B: activating non-kinase domain mutations), and 3.8% (cohort C: kinase domain mutations).
• Median PFS was 4.5 months (cohort A) and 3.7 months (cohort B). Median DoR was 7.8 months (A) and 6.9 months (B). Median OS was 17.5 months (A) and 11.4 months (B).
• Hyperphosphatemia and stomatitis were common adverse events. TP53 co-mutations correlated with lack of response, while BAP1 alterations predicted higher response rates.

Conclusions:

• Pemigatinib demonstrates clinical activity in FGFR-altered advanced solid tumors, particularly those with fusions/rearrangements.
• The study identified potential predictive markers (BAP1) and resistance mechanisms (gatekeeper/molecular brake mutations), expanding the scope of FGFR inhibition.
• Further investigation into novel therapeutic areas and drug failure mechanisms is warranted.