Safety and efficacy of dostarlimab monotherapy as first-line treatment in programmed cell death-ligand 1–positive recurrent/metastatic head and neck squamous cell carcinoma: Results from a phase 2 trial.

6037 Background: The use of immune checkpoint inhibitors (ICIs) in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has improved patient outcomes and showed benefit in the perioperative setting. The GALAXIES H&N-202 study (NCT06062420) evaluated novel immunotherapy combinations versus dostarlimab monotherapy in patients with R/M programmed cell death-ligand 1 (PD-L1)-positive HNSCC. Here, we present updated safety and efficacy results for patients who received dostarlimab monotherapy. Methods: GALAXIES H&N-202 is a multicenter, open-label, randomized, Phase 2 study assessing immunotherapy as monotherapy or in combination as first-line treatment (1L) in adults with R/M PD-L1-positive (combined positive score [CPS] ≥1) HNSCC. The dostarlimab monotherapy arm comprised patients randomized to receive dostarlimab 500 mg every 3 weeks until progression, unacceptable toxicity, death, or withdrawal. Investigator-confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 was the primary endpoint, and safety was a secondary endpoint. Outcomes were analyzed descriptively. Results: At data cutoff (July 14, 2025), 66 patients were enrolled in the dostarlimab monotherapy arm. All patients had ≥4.5 months of follow-up from first dose. The mean patient age was 64.7 years, 80% were male, and 53% had lung metastases. After a median treatment duration of 19.0 weeks (range: 3.0–69.0), ORR was 27.3% (95% confidence interval [CI]: 17.0, 39.6) overall and 42.4% (25.5, 60.8) for those with a CPS ≥20 (Table), and median PFS (95% CI) was 4.2 (2.7, 5.8) and 7.8 (3.0, NE) months, respectively. Treatment-emergent adverse events (TEAEs) occurred in 59 (91%) patients and treatment-related adverse events (TRAEs) in 33 (51%) patients. Three (5%) patients discontinued treatment due to TEAEs. Grade ≥3 TEAEs were reported in 21 (32%) patients and Grade ≥3 TRAEs in 3 (5%) patients. Seventeen (26%) patients experienced serious adverse events (SAEs) and 3 (5%) experienced treatment-related SAEs. Fatal SAEs were reported in 7 (11%) patients; none were treatment related. Conclusions: Dostarlimab monotherapy showed encouraging antitumor activity, particularly in patients with a CPS ≥20, and a consistent safety profile in 1L R/M HNSCC that is comparable to other ICIs in HNSCC. Clinical trial information: NCT06062420 . Efficacy outcomes. Confirmed ORR per RECIST v1.1, n (%) [95% CI] n=66 CPS ≥20 (n=33) 14 (42.4) [25.5, 60.8] CPS 1–19 (n=33) 4 (12.1) [3.4, 28.2] Overall 18 (27.3) [17.0, 39.6] Best response, n (%) n=66 Complete response 1 (1.5) Partial response 17 (25.8) Stable disease 23 (34.8) Progressive disease 17 (25.8) Not evaluable 8 (12.1) CI, confidence interval; CPS, combined positive score; ORR, objective response rate; RECIST, Response Evaluation Criteria in Solid Tumors.