A Phase 2 Study of Pemigatinib for Pre-Treated Glioblastoma or Other Gliomas with Activating FGFR1-3 Alterations: Results from FIGHT-209.

2003 Background: FGFR genomic alterations occur in approximately 8% of gliomas. Inhibition of FGFR1-3 with pemigatinib showed antitumor activity in a multihistology basket trial (FIGHT-207) in which approximately 10% of participants (pts) had recurrent/progressive FGFR-altered glioblastoma (GBM). We further investigated pemigatinib activity in primary brain tumors by conducting an international, multicenter, single-arm, 2-cohort, phase 2 study specifically in adults with FGFR-altered pretreated gliomas (FIGHT-209; NCT05267106). Methods: Pts were enrolled in 2 cohorts: A, histologically or molecularly defined GBM; or B, other gliomas, glioneuronal tumors, and neuronal tumors. Eligible pts had tumors harboring a FGFR1-3 fusion/rearrangement or mutation detected by an accredited laboratory that had recurred/progressed after ≥1 prior therapy. Pemigatinib (oral, 13.5 mg on days 1-14/21) was intended to continue until progression by Response Assessment in Neuro-Oncology (RANO) criteria determined by an independent review committee (IRC) or unacceptable toxicity. Efficacy of each cohort was evaluated independently. The primary endpoint was objective response rate (ORR; partial plus complete) per RANO (cohort A), with a goal of > 28%. Key secondary and exploratory endpoints were ORR in cohort B, ORR by investigator assessment, progression-free survival (PFS) by IRC, overall survival (OS), safety, neurologic function by Neurologic Assessment in Neuro-Oncology (NANO), and efficacy correlations with diagnosis and specific FGFR-alterations. Results: Between May 2022 and December 2023, 74 pts were enrolled in cohort A and 9 in cohort B. FGFR1-3 fusions/rearrangements were the most common genomic alterations in cohort A (n = 65 [88%]) and in cohort B, FGFR1 mutations (n = 8 [89%]). Pts had a median (range) age of 56 (20-79) years; 60% were male. On September 27, 2024 (data cutoff), 16 pts remained on treatment (cohort A, n = 11 [15%]; cohort B, n = 5 [56%]); 67 discontinued, primarily due to progressive disease (n = 59 [71%]). In cohort A, ORR was 8% (6 partial responses [PR], 0 complete responses [CR]); 21 pts (28%) had stable disease (SD); estimated 6-month PFS rate was 17% (95% CI, 8.7-27.8) and 12-month OS rate 48% (95% CI, 35.6-60.2). In cohort B, the ORR was 22% (1 CR, 1 PR); 3 (33%) SD. Most treatment-emergent adverse events (AEs) were low grade in severity (grade ≥3, 36.1%). Hyperphosphatemia, a class effect of FGFR inhibitors, was the most common AE (75%); 6 pts (7%) required dose reduction and 4 pts (5%) discontinued due to AEs. Conclusions: ORR did not meet the pre-specified goal of > 28% among pts with GBM harboring pemigatinib-sensitizing FGFR alterations. However, durable disease stabilization was observed, notably in pts with CNS tumors other than GBM, and toxicities were manageable. More mature PFS and OS data will be presented with exploratory molecular correlations. Clinical trial information: NCT05267106 .