Mitazalimab Plus mFOLFIRINOX Delivers High ORR in Previously Untreated Metastatic Pancreatic Cancer

Adding mitazalimab to mFOLFIRINOX led to a 52% objective response rate (ORR) as frontline therapy in 23 patients with metastatic pancreatic cancer, according to findings from a preplanned interim analysis of the phase 2 OPTIMIZE-1 trial (NCT04888312).¹

In a prior study, treatment with FOLFIRINOX led to an ORR of 31.6% in a similar patient population.²

Additional findings indicated that the disease control rate was greater than 90%. Safety data were in line with those from the phase 1b dose-escalation portion of the trial, in which the combination was safe and well tolerated at the recommended phase 2 dose of 900 μg/kg.

Based on these findings, Alligator Bioscience plans to pursue discussions with regulators in the United States and Europe regarding accelerated approval pathways while continuing enrollment in the trial. Investigators hope to release topline data from the trial in the first quarter of 2024.

“We are thrilled with these interim results, which demonstrate that mitazalimab combined with chemotherapy could offer a significant clinical benefit for pancreatic cancer patients over standard of care,” Søren Bregenholt, Alligator’s chief executive, said in a news release. “We are very keen to progress our lead asset through the next stage of its development as quickly as we can, and we look forward to discussing with regulatory authorities the potential accelerated development and approval pathway for mitazalimab in pancreatic cancer. These strong interim data reconfirm out commitment to mitazalimab and supports broadening the mitazalimab clinical development program in additional tumor types.”

Mitazalimab is a human CD40 agonistic IgG1 antibody that targets CD40, jumpstarting cancer immunity by recruiting dendritic cells, which leads to tumor-specific T-cell priming and activation. Additionally, CD40 agonists on malignant pancreatic myeloid cells promote degradation of the desmoplastic tumor stroma, improving influx of T cells and chemotherapeutic agents into the tumor.

Mitazalimab has shown to be safe and well tolerated at doses up to 1200 μg/kg, with antitumor activity signs in patients with solid tumors enrolled in a phase 1 study (NCT02829099). Additionally, most treatment-related adverse effects (TRAEs) were grade 1 or 2.³

OPTIMIZE-1 is an open-label, multi-center study evaluating the safety and efficacy of the CD40-directed monoclonal antibody mitazalimab in combination with mFOLFIRINOX in treatment-naïve patients with metastatic pancreatic cancer.

To be eligible for enrollment, patients must be at least 18 years of age and have received a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma with a life expectancy of at least 3 months. Patients also should not have received prior chemotherapy or abdominal radiotherapy and have acceptable hematologic and clinical chemistry laboratory values.⁴

The primary end point is the frequency of dose-limiting toxicities and ORR. Key secondary end points include progression-free survival, overall survival, and safety.

In prior safety findings from the phase 1b portion of the trial presented at the 2022 ASCO Annual Meeting, 5 patients with histologically confirmed, previously untreated metastatic pancreatic cancer received 450 µg/kg of mitazalimab.³

Two patients were female, and 3 were male, with a median age of 65 years (range, 60-68) and an ECOG score of 0 or 1. The median time since primary diagnosis was 13 days (range, 7-82).

TRAEs were grade 1 or 2 (n = 4/5). TRAEs occurring in at least 1 patient were fever, muscle pain, and nausea. No dose-limiting toxicities were reported, and no patients required dose interruption or reduction with either mitazalimab or mFOLFIRINOX.

Two patients discontinued treatment because of disease progression and three remain on study.

“We are pleased with the signs of clinical activity observed in the OPTIMIZE-1 interim analysis and believe that mitazalimab in combination with chemotherapy warrants continued development for the treatment of pancreatic cancer patients, which is an area of high unmet need,” Professor Jean-Luc van Laethem, MD, PhD, coordinating principal investigator, Erasmus University Hospital, Brussels, said. “We will continue enrolment, treatment and follow-up of patients to further characterize the progression-free and overall survival, as the study continues.”

References

1. Alligator Bioscience announces positive interim results from mitazalimab OPTIMIZE-1 phase 2 trial in pancreatic cancer exceeding 50% objective response rate. News release. January 2, 2023. Accessed January 5, 2023. https://bit.ly/3WM7s39
2. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-25. doi:10.1056/NEJMoa1011923
3. Van Laethem JL, Borbath I, Prenen H, et al. Mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (PDAC): Safety data from part of the OPTIMIZE-1 study. J Clin Oncol. 2022;40(suppl 16):e16237. doi:10.1200/JCO.2022.40.16_suppl.e16237
4. Safety and efficacy of mitazalimab in combination with chemotherapy in pancreatic cancer patients (OPTIMIZE-1). ClinicalTrials.gov. Updated December 7, 2022. Accessed January 5, 2022. https://clinicaltrials.gov/ct2/show/NCT04888312