Final Data Show Continued Responses, Safety by Mitazalimab in Pancreatic Cancer

Mitazalimab, in combination with standard chemotherapy, has exhibited continued promising efficacy and safety in treating metastatic pancreatic cancer, according to a final readout of data from the phase 1b/2 OPTIMIZE-1 trial (NCT04888312).¹

In the latest 30-month data report, with a median follow-up period of 33 months, the agent demonstrated a strong, durable response in line with trends evident from earlier reports, meeting its primary end point with a final objective response rate (ORR) of 54.4% (42.1% confirmed) and a median duration of response of 12.6 months. Moreover, in terms of survival, the 30-month overall survival (OS) rate was 21%, highlighting a sizable proportion of the patient population who survived beyond 2 years. Together with a median progression-free survival of 7.8 months and median OS of 14.9 months, the final data underscore the potential of the agent to achieve sustained activity and survival in a difficult-to-treat cancer with overall poor prognosis.

Previously, in an interim readout of phase 2 data, the study had met the primary end point with an ORR of 52%, resulting in an FDA orphan drug designation for pancreatic cancer by the FDA in 2023. Further efficacy and safety data at 24 months follow-up were presented at the European Society for Medical Oncology (ESMO) 2025 Gastrointestinal Cancers Congress in Barcelona, Spain, including a 24-month survival rate of 29.4% and dose-response relationship that reinforces the agent’s manageable safety profile.²

“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,” stated Søren Bregenholt, chief executive officer of Alligator Bioscience, in a press release.¹

OPTIMIZE-1 is a single-arm, open-label, multicenter study assessing the clinical efficacy and safety of mitazalimab, a CD40 agonistic IgG1 antibody,³ plus modified FOLFIRINOX (mFOLFIRINOX) chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma.⁴ Phase 1b was the dose-determining stage of the study, where 900 μg/kg was selected as the recommended phase 2 dose for mitazalimab over 450 μg/kg. The objective of phase 2 was to assess the clinical efficacy of mitazalimab administered intravenously at the recommended dose, in combination with mFOLFIRINOX chemotherapy.

What Are the Next Steps for OPTIMIZE-1?

With phase 2 coming to a close, Alligator Bioscience, the sponsor, is looking forward to advancing the agent to a pivotal phase 3 trial, which will generate further confirmatory evidence of the encouraging trends seen so far. While a protocol for phase 3 has not yet been released, the sponsor has confirmed that a dose of 900 μg/kg was selected for phase 3 and endorsed by the FDA based on dose characterization data from the trial, also presented at the 2025 ESMO Gastrointestinal Cancers Congress.^2,5 As the phase 2 results are derived from a single-arm study, a controlled design will be necessary to confirm the validity of prior findings.

“OPTIMIZE-1 has now successfully fulfilled it[s] purpose and will be winding down following these final results … we remain well prepared to initiate a confirmatory [p]hase 3 trial together with a partner. We look forward to bringing this important therapy one step closer to patients,” Bregenholt shared.¹

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://tinyurl.com/3845ve3c

2. Alligator to present 24-month OPTIMIZE-1 data at ESMO GI 2025. News release. Alligator Bioscience. July 1, 2025. Accessed September 25, 2025. https://tinyurl.com/mvxmwcnx

3. Van Laethem JL, Borbath I, Prenen H, et al. Combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (OPTIMIZE-1): a single-arm, multicentre phase 1b/2 study. Lancet Oncol. 2024;25(7):853-864. doi:https://doi.org/10.1016/s1470-2045(24)00263-8

4. 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://clinicaltrials.gov/study/NCT04888312

5. Alligator Bioscience receives FDA endorsement of mitazalimab Phase 3 dose for pancreatic cancer. News release. Alligator Bioscience. Published June 13, 2025. Accessed September 25, 2025. https://tinyurl.com/rp9ajxbh