FDA Grants Orphan Drug Designation to Mitazalimab for Pancreatic Cancer

The FDA has granted an orphan drug designation (ODD) to mitazalimab for the treatment of patients with pancreatic cancer, according to Alligator Biosciences.¹

Mitazalimab is a CD40-directed monoclonal antibody developed to sensitize tumors to chemotherapy and induce immune-mediated cell death through the activation of dendritic cells, B cells, and macrophages.

Positive findings from the phase 2 OPTIMIZE-1 trial (NCT04888312) evaluating the agent in combination with modified FOLFIRINOX (mFOLFIRINOX) in treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma support the ODD.

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

“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.¹ “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.”

Image Credit: © SciePro [stock.adove.com]

The open-label, multi-center OPTIMIZE-1 study is assessing the efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma.³

Patients must be aged 18 years or older with an ECOG performance status of 0 or 1, measurable disease per RECIST v. 1.1, a life expectancy of ≥ 3 months, and acceptable hematologic laboratory values to be eligible for enrollment. Additionally, patients must not have received previous chemotherapy for pancreatic ductal adenocarcinoma or prior abdominal radiotherapy, excluding palliative radiotherapy to non-target lesions.

The first part of the trial evaluated 2 dose levels of mitazalimab given at 450 ug/kg and 900 ug/kg combined with mFOLFIRINOX to determine the recommended phase 2 dose of the combination. In the expansion part, investigators are assessing the clinical efficacy of mitazalimab plus mFOLFIRINOX using a Simon's two-stage design.

The primary end points of the study are incidence of dose limiting toxicities and ORR, and secondary end points include type, frequency and severity of adverse events, pharmacokinetics, anti-tumor Activity per RECIST 1.1, PFS, and OS.

Additional interim data, including results on PFS, are anticipated to be announced in mid-2023. Full topline data are expected in the first quarter of 2024.¹ The FDA will utilize these data and this ODD to aid in further discussions regarding the clinical development and approval pathway for mitazalimab in this patient population.

REFERENCES:

1. Alligator Bioscience receives FDA orphan drug designation for mitazalimab in pancreatic cancer. News release. Alligator Bioscience. May 18, 2023. Accessed May 23, 2023. https://bit.ly/43ghMTE

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 23, 2023. https://bit.ly/3BRvZec

3. Safety and efficacy of mitazalimab in combination with chemotherapy in pancreatic cancer patients (OPTIMIZE-1). ClinicalTrials.gov. Updated April 24, 2023. Accessed May 23, 2023. https://clinicaltrials.gov/ct2/show/NCT04888312