Mitazalimab/Chemo Yields Promising Survival/Responses in Untreated PDAC

At 30 months, mitazalimab plus mFOLFIRINOX achieved an OS rate of 21% in patients with previously untreated metastatic PDAC.

Mitazalimab plus leucovorin, fluorouracil, irinotecan, and oxaliplatin at modified dosages (mFOLFIRINOX) continued to demonstrate promising and durable clinical activity compared with standard chemotherapy as treatment for patients with previously untreated metastatic pancreatic cancer in a 30-month analysis of the phase 1b/2 OPTIMIZE-1 trial (NCT04888312), according to a press release from the developer, Alligator Bioscience.1

With a median follow-up of 33 months, the 30-month overall survival (OS) rate was 21%, with 2 patients remaining on treatment and 8 in long-term survival follow-up; notably, this final readout confirmed data maturity. At 12, 18, and 24 months, the OS rate was 58%, 37%, and 26%, respectively. The median OS was 14.9 months. The median progression-free survival (PFS) was 7.8 months.

The objective response rate (ORR) was 54.4%, with 42.1% of responses confirmed; the median duration of response was 12.6 months.

OPTIMIZE-1 was an open-label, multicenter trial that evaluated the clinical efficacy of mitazalimab with chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC).

Previously, in July 2024, results from the trial were published in The Lancet Oncology.2 Additionally, at the 2025 American Society of Oncology (ASCO) Annual Meeting, an analysis of biomarkers associated with outcomes from the trial was presented.3

The biomarker analysis demonstrated that intratumoral myeloid cells and T cells were activated in responding patients. Furthermore, a novel, potentially predictive fibrosis-related gene signature was associated with improved OS.

“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 at Alligator Bioscience.1 “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.”

A total of 70 patients were enrolled on the trial between September 2021 and March 2023. The recommended phase 2 dose of mitazalimab was identified to be 900 μg/kg in the phase 1b portion of the trial; 5 patients received 450 μg/kg of mitazalimab, and the rest received 900 μg/kg. Dosing for mFOLFIRINOX included 85 mg/m2 of oxaliplatin, 400 mg/m2 of leucovorin, 150 mg/m2 of irinotecan, and 2400 mg/m2 of fluorouracil. In cycle 1, which was a 21-day cycle, mitazalimab was given on days 1 and 10, and mFOLFIRINOX was given on day 8; in subsequent cycles, which were 14 days long, mitazalimab was given 2 days following mFOLFIRINOX.

Eligible patients were at least 18 years old with a diagnosis of histologically documented, previously untreated metastatic PDAC; additionally, patients had an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 criteria, no receipt of prior chemotherapy, no receipt of prior abdominal therapy, and a life expectancy of at least 3 months.4

Patients were excluded from trial participation if they had other types of non-ductal tumors of the pancreas, other current cancer or history of cancer in the 3 years prior to enrollment, known central nervous system metastases, contraindication to any constituent of study treatment, or uncontrolled intercurrent illness, among other reasons.

The trial’s primary end point in phase 1b was the incidence of dose-limiting toxicities; in phase 2, the primary end point was ORR. Secondary end points included the type, frequency, and severity of adverse events; tolerability; pharmacokinetics; PFS; and OS.

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 22, 2025. https://tinyurl.com/2hbkc8mt
2. 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:10.1016/S1470-2045(24)00263-8
3. Cassier PA, Van Laethem JL, Borbath I, et al. Biomarkers associated with outcomes from OPTIMIZE-1: CD40 agonist mitazalimab with mFOLFIRINOX in patients with untreated metastatic pancreatic cancer. J Clin Oncol. 2025;42(suppl_16):4133. doi:10.1200/JCO.2024.42.16_suppl.4133
4. Safety and efficacy of mitazalimab in combination with chemotherapy in pancreatic cancer patients (OPTIMIZE-1). ClinicalTrials.gov. Updated January 13, 2025. Accessed September 22, 2025. https://tinyurl.com/49bxk6db