FDA Gives Orphan Drug Designation to Mitazalimab in Pancreatic Cancer

Mitazalimab is a monoclonal antibody that targets CD40, thereby potentially sensitizing tumors to chemotherapy and attacking tumors by activating dendritic cells, B cells, and macrophages.

The FDA has granted orphan drug designation to the investigational CD40 monoclonal antibody mitazalimab as a treatment for patients with pancreatic cancer, according to a press release from Alligator Bioscience.¹

Investigators are currently assessing mitazalimab plus modified leucovorin calcium/folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) in the treatment of those with metastatic pancreatic ductal adenocarcinoma (PDAC) as part of the phase 2 OPTIMIZE-1 trial (NCT04888312). An interim analysis in January 2023 highlighted an objective response rate (ORR) of 52% among 23 evaluable patients based on RECIST v1.1 criteria.² The regimen also yielded a disease control rate of 90%.

In April 2023, investigators announced that they had completed patient enrollment for the OPTIMIZE-1 trial.³

The developers of mitazalimab plan to convene with American and European regulators to discuss the agent’s development and approval pathway in pancreatic cancer later in 2023. Additionally, investigators aim to share interim progression-free survival (PFS) and overall survival (OS) findings from the OPTIMZE-1 trial in mid-2023 as well as topline data in the first quarter of 2024.

“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 at Alligator Bioscience, said in the press release.

Mitazalimab is a monoclonal antibody that targets CD40, thereby potentially sensitizing tumors to chemotherapy and attacking tumors by activating dendritic cells, B cells, and macrophages.

In the multi-center, open-label phase 2 OPTIMIZE-1 trial, previously untreated patients with metastatic PDAC received mitazalimab intravenously every 14 days in combination with mFOLFIRINOX.

The primary end points of the OPTIMIZE-1 trial include the incidence of dose-limiting toxicities and ORR. Secondary end points include PFS, OS, anti-tumor activity per RECIST v1.1 guidelines, the incidence of adverse effects, and the pharmacokinetics of mitazalimab.

Patients 18 years and older with histologically documented, previously untreated metastatic PDAC and an ECOG performance status of 0 or 1 were eligible to enroll on the trial. Additional eligibility criteria included having measurable disease based on RECIST v1.1 guidelines, a life expectancy of at least 3 months, no receipt of previous chemotherapy for PDAC, and no prior abdominal radiotherapy.

Patients with other types of non-ductal pancreatic tumors, other current cancer, known central nervous system metastases, or carcinomatous meningitis were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had a history of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction; uncontrolled intercurrent illness including active infection; or a known history of human immunodeficiency virus, hepatitis B, or active hepatitis C infection.

Receiving an attenuated vaccine within 28 days before beginning study treatment or any prior treatment with irinotecan or platinum-containing chemotherapy, having pre-existing peripheral neuropathy higher than grade 1, known Gilbert’s disease, or known fructose intolerance were also grounds for exclusion from the trial.

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. bit.ly/43qcPb7
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. bit.ly/3GHIoo5
3. 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. News release. April 12, 2023. Accessed May 23, 2023. bit.ly/3Ou2ero