Promising first results of mitazalimab in metastatic pancreatic ductal adenocarcinoma

Presented by

Dr Teresa Macarulla, Vall d’Hebron University Hospital, Spain

Conference

ESMO GI 2024

Trial

Phase 1/2, OPTIMIZE-1

Doi
https://doi.org/10.55788/ecca8a13

The anti-CD40 antibody mitazalimab in combination with mFOLFIRINOX demonstrated a manageable safety profile and promising clinical efficacy in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) in the phase 1/2 OPTIMIZE-1 trial.

With a 5-year overall survival (OS) rate below 5%, current systemic therapies for mPDAC are associated with poor outcomes. Previously, CD40 agonists were shown to alter macrophage phenotype polarisation to favour the M1 phenotype and suppress pancreatic cancer [1].

The phase 1/2 OPTIMIZE-1 trial (NCT04888312) explored the safety and efficacy of mitazalimab, a second-generation CD40 agonist, combined with modified FOLFIRINOX in mPDAC patients. The primary endpoint was overall response rate (ORR); secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Dr Teresa Macarulla (Vall d’Hebron University Hospital, Spain) presented the first results [2].

In phase 1b of OPTIMIZE-1, 900 µg/kg mitazalimab was determined to be the recommended phase 2 dose. A total of 70 patients were enrolled in phase 2 (efficacy set: n=57; safety set: n=70). After a median follow-up of 18 months, confirmed ORR was 42.1%. Median DoR was 12.6 months, median PFS was 7.7 months, and median OS was 14.9 months. A high CD4 effector T-cell expansion after the first cycle of mitazalimab correlated with a better median OS.

Treatment-emergent adverse events (TEAEs) of grade ≥3 were observed in 55 (79%) participants, with neutropenia (25.7%), hypokalemia (15.7%), and thrombocytopenia (11.4%) being the most common. Safety was overall consistent with the known mFOLFIRINOX safety profile.

Based on these results, Dr Macarulla concluded that “mitazalimab in combination with mFOLFIRINOX demonstrated a well-manageable safety profile and a promising clinical efficacy. These encouraging results warrant continued development in a randomised phase 3 trial.”

Lim CY, et al. Gut Liver. 2022;16:645-659.
Macarulla T, et al. CD40 agonist mitazalimab combined with mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Primary analysis of the OPTIMIZE-1 phase 1b/2 study. Abstract 280MO, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.

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