KEY TAKEAWAYS
- The OPTIMIZE-1 phase 1 & 2 trial aimed to investigate the safety and efficacy of mitazalimab combined with mFOLFIRINOX in pts with mPDAC.
- The primary endpoint was to determine ORR.
- Researchers noticed significant efficacy in terms of survival benefit and immune activation; further investigation is ongoing.
With a 5-year overall survival (OS) rate <5%, systemic therapies for metastatic pancreatic ductal adenocarcinoma (mPDAC) are associated with poor outcomes.
Teresa Macarulla Mercade and the team aimed to assess the safety and efficacy of mitazalimab, a human CD40 agonistic IgG1 antibody, combined with mFFX in mPDAC patients (pts).
They performed an inclusive analysis in OPTIMIZE-1, an open-label, single-arm, multicenter, phase 1b/2 study. Newly diagnosed, chemotherapy-naïve pts with metastatic pancreatic ductal adenocarcinoma (mPDAC) received mitazalimab on day 1, followed by a 2-week dosing regimen starting with mFOLFIRINOX on day 8 and mitazalimab on day 10. Phase 1b established 900 μg/kg as the recommended phase 2 dose of mitazalimab. The phase 2 primary endpoint assessed overall response rate (ORR), with secondary endpoints including safety, duration of response (DoR), progression-free survival (PFS), and OS.
About 70 pts received either 450 μg/kg (n=5) or 900 μg/kg (n=65) of mitazalimab in combination with mFFX. Common treatment emergent adverse events (TEAEs) of Grade ≥3 included neutropenia (25.7%; 18 pts), hypokalemia (15.7%; 11 pts), anemia and thrombocytopenia (11.4%; 8 pts), consistent with the safety profile of mFFX. Four pts (5.7%) discontinued treatment due to TEAEs. Among the 57 evaluable pts treated with the 900 μg/kg dose of mitazalimab, the confirmed ORR was 40.4%, with 22 pts achieving partial responses and 1 patient achieving a complete response.
Additionally, 22 pts achieved stable disease, resulting in a disease control rate of 78.9%. The unconfirmed ORR was 50.9%. Median DoR was 12.5 months, median progression-free survival (mPFS) was 7.7 months (with a 6-month PFS of 62.4%), and median overall survival (mOS) was 14.3 months (with a 1-year OS of 59.3%). Increases in CD38+ NKT cells after the first mitazalimab infusion correlated significantly with the depth of response, with similar trends observed in CD38+ and Ki67+ CD8 T cell populations. Tumor mutational burden was not associated with any endpoints.
The study concluded that the OPTIMIZE-1 trial achieved its primary endpoint, demonstrating a manageable safety profile and promising DoR linked to significant survival benefits. The activation profile of NKT and T cells indicates a potential role for mitazalimab in fostering robust anti-tumor responses. These compelling findings support advancing to a randomized phase 3 study for further validation and clinical integration.
The trial was sponsored by the Alligator Bioscience AB.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT04888312
Mercade T.M., Borbath I, Geboes K, et al. (2024). “280MO – CD40 agonist mitazalimab combined with mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Primary analysis of the OPTIMIZE-1 phase Ib/II study.” Presented at ESMO-GI 2024 (Abstract 280MO).
