Abstract
BACKGROUND: Erda is an oral selective pan-FGFR tyrosine kinase inhibitor approved to treat adults with locally advanced/metastatic urothelial carcinoma with susceptible FGFR3/2alt who have progressed during/after ≥1 line of platinum-based chemotherapy. RAGNAR interim results demonstrated tumor-agnostic efficacy in adults/adolescents with previously-treated advanced solid tumors with prespecified FGFRalt. Here we report results for patients with HGG/LGG. METHODS: Patients with HGG/LGG harboring prespecified FGFR1-4alt (mutations/fusions), disease progression after ≥1 line of systemic therapy, and who exhausted standard therapies received oral erda until disease progression or intolerable toxicity. Primary endpoint: ORR by independent review committee (IRC). Secondary endpoints: DOR, disease control rate (DCR), investigator-assessed efficacy, and safety. Response was based on RANO criteria. RESULTS: At data cutoff, 37 HGG (n = 30)/LGG (n = 7) patients received erda. In HGG (glioblastoma, n = 25 [83%]; median (m) age 54.5y [range 13-70]), 29 (97%) had FGFR fusions (FGFR3-TACC3, n = 24); all (100%) underwent initial resection (if feasible) and received radiotherapy/chemotherapy per institution (eg, Stupp protocol); patients received median 2 prior therapies (range 1-6; 37% with prior bevacizumab). ORR in HGG was 10% by IRC (95%CI, 2-27) and 20% by Investigator (95%CI, 8-39); mDOR was not reached (m-F/U, 18.0mo); DCR was 57% (95%CI, 37-75). In LGG (m-age 22y; range 12-32), 4 (57%) had FGFR1 mutation (all FGFR1-K656E); 3 (43%) had FGFR fusion. ORR in LGG was 29% by IRC (95%CI, 4-71) and 14% by Investigator (95%CI, 0-58); mDOR was not reached; DCR was 71% (95%CI, 29-96). 17 HGG patients (57%) had TERT co-alterations; 9 (30%) had PTEN deletions. No HGG/LGG patients had IDH1/2 mutations. Most common (≥40%) adverse events (AEs): hyperphosphatemia, diarrhea, dry skin, dry mouth. 43% had serious AEs (treatment-related, 16%). 19% discontinued due to AEs. No treatment-related deaths occurred. CONCLUSIONS: Erda demonstrated clinically meaningful activity in heavily pre-treated HGG/LGG with FGFRalt. Safety was consistent with known safety profile of erda.