Dostarlimab monotherapy produced a 27% response rate in PD-L1–positive recurrent/metastatic head and neck squamous cell carcinoma
First-line dostarlimab-gxly (Jemperli) monotherapy produced an investigator-assessed confirmed objective response rate (ORR) of 27% (95% CI, 17%-40%) in patients with PD-L1–positive recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), according to updated data from the phase 2 GALAXIES H&N-202 trial (NCT06062420) presented in a poster session during the
The ORR was higher among patients with a PD-L1 combined positive score (CPS) of 20 or higher, at 42% (95% CI, 26%-61%), compared with 12% (95% CI, 3%-28%) in those with a CPS of 1 to 19. Median progression-free survival was 4 months (95% CI, 3-6) in the overall population, 8 months (95% CI, 3-not reached) in the subgroup with a CPS of 20 or greater, and 3 months (95% CI, 2-4) in the subgroup with a CPS of 1 to 19.
GALAXIES H&N-202 was a multicenter, open-label, randomized phase 2 platform trial that evaluated dostarlimab as monotherapy or in combination with investigational immune checkpoint inhibitors as first-line treatment in adults with PD-L1–positive (CPS, ≥ 1) recurrent/metastatic HNSCC.1,2
Previously untreated patients were randomly assigned to dostarlimab monotherapy at 500 mg (n = 60) or to 1 of 4 combination substudies, which were not included in this analysis.1 Random assignment was stratified by PD-L1 expression (CPS 1-19 vs CPS ≥ 20) and HPV/oropharyngeal status. The primary end point was investigator-assessed confirmed ORR.
At the July 14, 2025, data cutoff, 66 patients were enrolled in the monotherapy arm and 65 had received treatment, with a minimum follow-up of 4.5 months. Median treatment exposure was 19 weeks (range, 3-69) over a median of 6 cycles (range, 1-23). Median patient age was 66 years (range, 41-89), 80% were male, and 50% had a CPS of 20 or higher. Disease was de novo metastatic in 20% of patients, a local regional recurrence in 29%, and a distant metastatic recurrence in 52%. The primary tumor was nonoropharyngeal in 61% of patients and oropharyngeal in 39%; among the oropharyngeal cancers, 8 (32%) were HPV positive and 18 (72%) were HPV negative or indeterminate.
Per RECIST 1.1, the investigator-assessed best response in the overall population was a complete response (CR) in 2% of patients, a partial response (PR) in 26%, stable disease (SD) in 35%, progressive disease in 26%, and not evaluable in 12%. In the subgroup with a CPS of 20 or greater, best responses included a CR in 3% of patients, a PR in 39%, and SD in 33%. In the subgroup with a CPS of 1 to 19, no CRs were reported and a PR occurred in 12% of patients. A waterfall analysis of maximum change in target lesion size showed more patients achieving a 30% or greater decrease in the subgroup with a CPS of 20 or greater than in the subgroup with a CPS of 1 to 19.
Treatment-emergent adverse effects (TEAEs) of any grade occurred in 91% of the 65 treated patients, with grade 3 or higher TEAEs in 32% and TEAE-related discontinuations in 5%. Treatment-related adverse effects (TRAEs) were reported in 51% of patients, with grade 3 or higher TRAEs in 5%; investigators noted that immune-mediated TRAEs were generally mild and consistent with prior experience with immune checkpoint inhibitors.
Serious adverse effects (SAEs) occurred in 26% of patients, including treatment-related SAEs in 5% (diarrhea, immune-mediated lung disease, and cytokine release syndrome, each in 1 patient). Fatal SAEs occurred in 11% of patients; none were considered treatment related. Grade 2 or higher immune-mediated TRAEs occurred in 18% of patients, most commonly hypothyroidism in 6%.
Investigators concluded that the safety profile was consistent with prior reports of dostarlimab in solid tumors and other PD-(L)1–targeting agents, with manageable toxicity and no treatment-related fatal events. Overall survival follow-up is ongoing.
The authors noted that these data support the continued investigation of dostarlimab in HNSCC, including in the phase 3 JADE trial (NCT06256588), which is evaluating sequential dostarlimab after chemoradiotherapy in patients with locally advanced, unresected PD-L1–positive disease.
