Mitazalimab Plus Chemo Demonstrates Potential OS Benefit in Previously Untreated Metastatic Pancreatic Cancer

Treatment with the combination of the CD40 agonist mitazalimab and modified FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and fluorouracil; mFOLFIRINOX) generated potentially favorable overall survival (OS) outcomes compared with historical controls in patients with previously untreated metastatic pancreatic cancer, according to final data from the phase 2 OPTIMIZE-1 trial (NCT04888312).¹

At a median follow-up of 33 months, patients treated with the combination experienced a median OS of 14.9 months. The OS rates at 12, 18, 24, and 30 months were 58%, 37%, 26%, and 21%, respectively.

Previously reported data showed the combination produced an objective response rate (ORR) of 54.4%, including a confirmed ORR of 42.1%. The median duration of response was 12.6 months, and the median progression-free survival was 7.8 months.

“The final OPTIMIZE-1 results reinforce our belief that mitazalimab has the potential to become a transformative treatment option for patients with pancreatic cancer, a disease with very limited therapeutic advances in decades,” Søren Bregenholt, chief executive officer at Alligator Bioscience, stated in a news release. “OPTIMIZE-1 has now successfully fulfilled its purpose and will be winding down following these final results. Hence, the costs continue to decrease as clinical sites close, while we remain well prepared to initiate a confirmatory phase 3 trial together with a partner. We look forward to bringing this important therapy one step closer to patients.”

How Was the OPTIMIZE-1 Trial Conducted?

OPTIMIZE-1 was an open-label, multicenter phase 1b/2 trial that enrolled patients at least 18 years of age with histologically documented, previously untreated metastatic pancreatic ductal adenocarcinoma who had measurable disease per RECIST 1.1 criteria and were naive to chemotherapy for pancreatic cancer.² Prior abdominal radiotherapy was not allowed, other than palliative radiotherapy directed at non-target lesions.

Other key inclusion criteria comprised an ECOG performance status of 0 or 1; a life expectancy of at least 3 months; and adequate hematologic function.

Investigators excluded patients with non-ductal pancreatic tumors, those with central nervous system metastases or carcinomatous meningitis, and patients with a history of myocardial infarction within 12 months of the first administration of mitazalimab.

During the dose-escalation portion of the study, mitazalimab was evaluated at doses of 450 µg/kg and 900 µg/kg given once every 2 weeks in combination with mFOLFIRINOX.³ The 900-µg/kg dose was selected for dose expansion.

The primary end points of the first portion of the study was to determine the recommended phase 2 dose of mitazalimab, with secondary end points including ORR and survival. In part 2, ORR was the primary end point. OS, PFS, best response, DOR, disease control rate, time to next therapy, safety, and pharmacokinetics were secondary end points.

What Is the Safety Profile of Mitazalimab Plus mFOLFIRINOX?

Data from the primary analysis of OPTIMIZE-1 presented at the 2024 ASCO Annual Meeting showed that in patients treated at the RP2D (n = 65), the rate of grade 3 or higher treatment-emergent adverse effects (TEAEs) was 80.0%. The most common grade 3 or higher TEAEs in the group included neutropenia (27.7%), hypokalemia (15.4%), anemia (12.3%), thrombocytopenia (12.3%), fatigue (10.8%), diarrhea (9.2%), peripheral neuropathy (7.7%), nausea (4.6%), and asthenia (4.6%).

In the overall safety-evaluable cohort (n = 70), TEAEs led to treatment discontinuation in 4 patients (5.7%). TEAEs that led to discontinuation included one patient with fatigue, chest pain, and headache; one patient with general deterioration of physical health; one patient with pneumonia; and one patient with pruritus.

References

1. Alligator announces final 30-month OPTIMIZE-1 results highlighting the potential of mitazalimab in metastatic pancreatic cancer. News release. Alligator Bioscience. September 22, 2025. Accessed September 24, 2025. https://alligatorbioscience.se/en/mfn_news/alligator-announces-final-30-month-optimize-1-results-highlighting-the-potential-of-mitazalimab-in-metastatic-pancreatic-cancer/
2. Safety and efficacy of mitazalimab in combination with chemotherapy in pancreatic cancer patients (OPTIMIZE-1). ClinicalTrials.gov. Updated January 13, 2025. Accessed September 24, 2025. https://www.clinicaltrials.gov/study/NCT04888312
3. Van Laethem J-L, Borbath I, Geboes KP, et al. OPTIMIZE-1 primary analysis: Safety, efficacy and biomarker results of a phase 1b/2 study combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). J Clin Oncol. 2024;42(suppl 16):4133. doi:10.1200/JCO.2024.42.16_suppl.4133