Manganese primed immunochemotherapy in platinum-resistant/refractory ovarian cancer: a randomized, single-blind, placebo-controlled, phase 2 trial

Abstract Platinum-resistant or refractory ovarian cancer (PROC) remains without immunotherapy approval and dismal prognosis, emphasizing the urgent need for novel therapies. This phase 2, single-blind, placebo-controlled, randomized trial evaluated the safety and efficacy of manganese chloride or placebo plus sintilimab, nab-paclitaxel and cisplatin in these patients. 84 patients were randomized to the Mn²⁺ (n=55) or placebo (n=29) arm. The primary endpoint of objective response rate (ORR) was met at 61.8% in the Mn²⁺ and 13.8% in placebo group. The secondary endpoints of median PFS (9.8 vs. 3.9 months), OS (21.4 vs. 7.9 months) and DOR (14.9 vs. 1.8 months) were significantly prolonged in the Mn²⁺ group. No significant differences in AEs and quality of life were document during the treatment period. The serum cytokines and scRNA-seq evidenced the cGAS-STING agonist function of Mn²⁺. Our study supported Mn²⁺-priming immunochemotherapy as a promising treatment regimen for PROC patients. ClinicalTrials.gov identifier: NCT03989336.