FDA Grants Orphan Drug Designation to Mitazalimab in Pancreatic Cancer

The FDA has granted an orphan drug designation to mitazalimab for use as a potential therapeutic option in patients with pancreatic cancer, according to an announcement from drug developer Alligator Biosciences.¹

Mitazalimab is a CD40-directed monoclonal antibody designed to sensitize tumors to chemotherapy and elicit immune-mediated cell death by activating dendritic cells, B cells, and macrophages. The safety and efficacy of the agent in combination with modified FOLFIRINOX (mFOLFIRINOX) is being evaluated in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma as part of the open-label, multicenter phase 2 OPTIMIZE-1 trial (NCT04888312).

“This designation is a key milestone for our lead asset mitazalimab, which is producing outstanding clinical results in its phase 2 trial in pancreatic cancer,” Søren Bregenholt, chief executive officer of Alligator Bioscience, stated in a press release. “Orphan designation confers significant benefits in the form of cost savings during development and marketing exclusivity following approval, and we are very pleased to see the potential of mitazalimab being recognized with the award of this designation.”

In January 2023, Alligator announced positive interim data from OPTIMIZE-1,² in which the addition of mitazalimab to mFOLFIRINOX led to an objective response rate (ORR) of 52% and disease control rate of more than 90% per RECIST v1.1 criteria in 23 evaluable patients. Additionally, the combination was shown to be safe and well tolerated at the recommended dose of 900 μg/kg in the phase 1b dose-escalation portion of the trial.

Early efficacy findings from the study compare favorably with those from an earlier phase 3 trial (NCT00112658), in which FOLFIRINOX produced an ORR of 31.6% as frontline therapy in patients with metastatic pancreatic cancer.³

In April 2023, Alligator announced that OPTIMIZE-1 had been fully enrolled.⁴ To be eligible for enrollment in the study, patients must have been at least 18 years of age, have received a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma, and have a life expectancy of at least 3 months. Patients also should have acceptable hematologic and clinical chemistry laboratory values. They should not have received prior chemotherapy or abdominal radiotherapy.⁵

The frequency of dose-limiting toxicities and ORR serve as the primary end points of the study. Secondary end points include progression-free survival, overall survival, and safety, among others.

Additional interim data, which will include results on PFS, are expected in mid-2023, and full topline data are anticipated in the first quarter of 2024.1 These data, coupled with this designation, will aid ongoing discussions with the FDA regarding further clinical development and the approval pathway for mitazalimab in pancreatic cancer.

References

1. Alligator Bioscience receives FDA orphan drug designation for mitazalimab in pancreatic cancer. News release. Alligator Bioscience. May 18, 2023. Accessed May 22, 2023. https://alligatorbioscience.se/en/news/alligator-bioscience-receives-fda-orphan-drug-designation-for-mitazalimab-in-pancreatic-cancer/
2. Alligator Bioscience announces positive interim results from mitazalimab OPTIMIZE-1 phase 2 trial in pancreatic cancer exceeding 50% objective response rate. News release. Alligator Bioscience. January 2, 2023. Accessed May 22, 2023. https://alligatorbioscience.se/en/news/alligator-bioscience-announces-positive-interim-results-from-mitazalimab-optimize-1-phase-2-trial-in-pancreatic-cancer-exceeding-50-objective-response-rate/
3. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825. doi:10.1056/NEJMoa1011923
4. Alligator Bioscience announces completion of patient enrollment in mitazalimab OPTIMIZE-1 phase 2 trial in pancreatic cancer and confirms timeline for top-line data in Q1 2024. News release. Alligator Bioscience. April 12, 2023. Accessed May 22, 2023. https://alligatorbioscience.se/en/news/alligator-bioscience-announces-completion-of-patient-enrolment-in-mitazalimab-optimize-1-phase-2-trial-in-pancreatic-cancer-and-confirms-timeline-for-top-line-data-in-q1-2024/
5. Safety and efficacy of mitazalimab in combination with chemotherapy in pancreatic cancer patients (OPTIMIZE-1). ClinicalTrials.gov. Updated April 24, 2023. Accessed May 22, 2023. https://clinicaltrials.gov/ct2/show/NCT04888312