Mitazalimab/Chemotherapy Yields Positive Responses in Metastatic PDAC

Investigators of the ongoing phase 2 OPTIMIZE-1 trial (NCT04888312) reported positive interim findings concerning the use of CD40 monoclonal antibody mitazalimab plus chemotherapy in the treatment of patients with metastatic pancreatic ductal adenocarcinoma, according to a press release from Alligator Bioscience.

Results from the trial indicated that mitazalimab with modified leucovorin calcium/folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) produced an objective response rate (ORR) of 52% in 23 evaluable patients per RECIST v1.1 criteria. Investigators also highlighted a disease control rate higher than 90%.

Mitazalimab plus mFOLFIRINOX was safe and well tolerated at the recommended dose of 900 μg/kg in the phase 1b dose escalation portion of the trial.

Based on these results, the manufacturers of mitazalimab plan to discuss a potential accelerated development and approval pathways for the regimen with American and European regulators for pancreatic cancer. Enrollment for the OPTIMZE-1 trial will continue and topline data are expected to be shared in early 2024.

“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 patients [with pancreatic cancer], which is an area of high unmet need,” coordinating principal investigator Jean-Luc van Laethem, MD, PhD a professor at Erasmus University Hospital, Brussels, said in the press release. “We will continue enrollment, treatment, and follow-up of patients to further characterize the progression-free survival (PFS) and overall survival (OS) as the study continues.”

Investigators of the open-label, multi-center phase 2 OPTIMIZE-1 trial are evaluating the efficacy and safety of mitazalimab plus mFOLFIRINOX in previously untreated patients with metastatic pancreatic ductal adenocarcinoma. Patients received mitazalimab intravenously every 14 days.

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

Patients 18 years and older with an ECOG performance status of 0 or 1 and a histologically documented diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma were eligible to enroll on the study. Additional inclusion criteria included having measurable disease per RECIST v1.1 criteria, not receiving previous chemotherapy or abdominal radiotherapy, and having a life expectancy of at least 3 months.

Patients were unable to enroll on the study if they had other types of non-ductal pancreatic tumors, other current cancer, known central nervous system metastases, or carcinomatous meningitis. Patients were also unsuitable for enrollment if they had a history of chronic diarrhea; a history of myocardial infarction within 12 months of beginning study treatment; uncontrolled intercurrent illness; known Gilbert’s disease; pre-existing peripheral neuropathy greater than grade 1; or a known history of human immunodeficiency virus, hepatitis B, or active hepatitis C infection.

“We are thrilled with these interim results, which demonstrate that mitazalimab combined with chemotherapy could offer a significant clinical benefit for patients [with pancreatic cancer] over standard-of-care [therapy],” Søren Bregenholt, chief executive officer at Alligator Bioscience, concluded.

Reference

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 January 5, 2023. bit.ly/3GHIoo5