OPTIMIZE-1 STUDY

Mitazalimab, a human CD40 agonistic IgG1 antibody, shows promise by reducing immune suppression, sensitising tumours to chemotherapy, and inducing long-lasting anti-tumour T-cell responses. The OPTIMIZE-1 study is a Phase 1b/2 open-label, multicenter study assessing mitazalimab’s safety and efficacy in combination with modified FOLFIRINOX (mFFX) in chemotherapy-naive metastatic pancreatic ductal adenocarcinoma (mPDAC) patients. The primary endpoint was the objective response rate (ORR) compared to a 30% ORR benchmark for FFX. Seventy mPDAC patients received mFFX plus mitazalimab.  Among the 57 patients at 900 mg/kg who received at least two treatment cycles and were evaluable for efficacy, the most common grade 3 or higher adverse events (AEs) included neutropenia (25.7%), anaemia (11.4%), hypokalemia (15.7%), and thrombocytopenia (11.4%), consistent with the known safety profile of FFX. Two patients discontinued treatment due to AEs.

23 patients (40.4%), including one complete responder, had confirmed objective responses. The median OS was 14.3 months, PFS was 7.4 months, and DoR was 12.5 months, with a median follow-up of 12.7 months. 

The results indicate that mitazalimab combined with mFFX is a feasible regimen with a manageable safety profile and promising efficacy, justifying further development in a confirmatory Phase 3 study.