Rogaratinib (pan-FGFR1–4 inhibitor) posts 41.7% ORR and 31.0-mo PFS in advanced SDH-deficient GIST

Rogaratinib (BAY 1163877) is an oral pan–fibroblast growth factor receptor (FGFR1–4) tyrosine kinase inhibitor intended to shut down the FGF3/FGF4→FGFR1 autocrine loop thought to be epigenetically activated in SDH-deficient GIST. In this Phase 2 cohort (NCT04595747) of advanced SDH-deficient gastrointestinal stromal tumor, 24 patients received rogaratinib, yielding 10 partial responses (ORR 41.7%), median PFS 31.0 months (95% CI 20.2–NR), and 1-year PFS 77.4% (95% CI 61.7–97.1); this compares favorably with later-line broad-spectrum GIST TKIs like regorafenib (median PFS 4.8 months in GRID) and ripretinib in ≥4L (median PFS 6.3 months; ORR ~9–12% in INVICTUS), although cross-trial comparisons are imperfect and SDH-deficient biology often differs from KIT/PDGFRA-mutant GIST. Toxicities were described as manageable, with expected on-target hyperphosphatemia plus fatigue and diarrhea, and cohort-wide phosphate elevations supported FGFR pathway engagement.