Aims: To characterize the alteration-type–dependent activity of gunagratinib, a selective irreversible pan-FGFR1–4 inhibitor, in patients with recurrent or metastatic head and neck cancer (R/M HNC) harboring FGF/FGFR alterations. Methodology: HNC patients from two prospective trials (ICP-CL-00301 Phase I and ICP-CL-00304 Phase IIa) were pooled. Patients with R/M HNC harboring FGF/FGFR alterations received oral gunagratinib monotherapy (14–22 mg in Study 301; 20 mg once daily in Study 304). The primary endpoint was ORR. Results: Thirty-seven patients (23 HNSCC, 9 nasopharyngeal carcinoma, 5 other histologies) were enrolled; 78.4% had received ≥3 prior systemic therapy lines, and 77.8% of Study 304 patients had received prior anti-PD-1/PD-L1 therapy. The confirmed ORR was 13.5% (95% CI, 4.5–28.8), with a DCR of 56.8%. The response pattern was alteration-type dependent: ORR was 50.0% for FGFR fusions, 22.2% for FGFR mutations, 16.7% for FGFR amplifications, and 7.7% for FGF3/4/19 amplifications. Median DoR was 11.0 months (95% CI, 7.1–NR); median PFS and OS were 4.1 and 7.4 months, respectively. In a sensitivity analysis at the RP2D (20 mg; n=27), ORR was 7.4%. Grade ≥3 treatment-related adverse events occurred in 35.1%; hyperphosphatemia was the most frequent event (70.3%), managed without discontinuation, and no treatment-related deaths occurred. Conclusion: In FGF/FGFR-altered R/M HNC, gunagratinib produced durable responses in patients with FGFR receptor-level alterations — particularly fusions or mutations — while the FGF3/4/19-amplified majority showed limited monotherapy activity but high disease control (65.4%), suggesting that combination strategies may be needed. Alteration type should guide patient selection for future FGFR-targeted trials.