Pemetrexed + pembrolizumab (antifolate chemo + PD-1) posts 75% clinical benefit but just 5% ORR in R/M adenoid cystic carcinoma

Pemetrexed (PTX; multitargeted antifolate chemotherapy) plus pembrolizumab (PMB; PD-1 inhibitor) was evaluated in the MC200708 single-arm Phase II trial (NCT04895735) in recurrent/metastatic adenoid cystic carcinoma (ACC) (n=20; 55% treatment-naïve; 75% no prior ICI). ORR was 5% (1/20 PR; DoR 12.4mo) with CBR 75% (1 PR + 14 SD), 1-year PFS 52.1% and 1-year OS 82.1% at 14.5mo median follow-up; this sits in the same “low-ORR, disease-stabilization” lane as VEGFR TKI approaches in ACC (e.g., lenvatinib monotherapy ORR ~15.6% with 75% SD in a Phase II trial), underscoring how hard it is for cytotoxics/IO alone to drive tumor shrinkage in ACC. Toxicity was non-trivial: grade ≥3 AEs in 80% (notably lymphopenia 40%, HTN 20%, fatigue 10%, pneumonitis 10%) with grade 4 events including lymphopenia and thrombotic thrombocytopenic purpura, and 23.5% discontinuation due to AEs.