Pemetrexed (antifolate chemo) + pembrolizumab (PD-1) delivers 37.5% ORR—and 63.6% in salivary duct carcinoma—in R/M salivary gland cancer

MC200708 (NCT04895735) is a single-arm Phase II (Simon two-stage) testing pemetrexed 500mg/m² IV q3w + pembrolizumab 200mg IV q3w in recurrent/metastatic non-adenoid cystic salivary gland cancers; any number of prior therapies were allowed (n=24 treated/eligible). Confirmed ORR was 37.5% (9/24; 95% CI 18.8–59.4) with median DoR 15.3mo, median PFS 6.2mo, and median OS 20.0mo; in salivary duct carcinoma (SDC) the ORR was 63.6%. Grade 3–4 toxicity occurred in 29.2% (mostly hematologic); reported grade 3–4 non-hematologic events included fatigue, rash, heart failure, hematuria, mastoiditis, hypokalemia—benchmarked against typical platinum/taxane regimens in mixed R/M SGC (ORR ~37–50%, mPFS ~5–6mo) and pembrolizumab monotherapy in PD-L1+ SGC (ORR ~12%), this combo looks at least “in-family” on PFS but notably higher on ORR (especially SDC), with a different toxicity mix.