Mitazalimab/Chemo Produces Enduring Responses in Metastatic PDAC

The FDA previously granted orphan drug designation to mitazalimab as a treatment for patients with pancreatic cancer in May 2023.

Combining the investigational CD40 monoclonal antibody mitazalimab with chemotherapy resulted in long-term responses in patients with metastatic pancreatic ductal adenocarcinoma (PDAC), according to a press release on findings from the second interim analysis of the phase 2 OPTIMIZE-1 trial (NCT04888312).¹

Treatment with mitazalimab plus chemotherapy increased the objective response rate (ORR) from 52% at the time of the original interim analysis in January 2023 to 57% in a population of 23 patients. Of the objective responders, 54% were receiving ongoing treatment for more than 10 months with sustained responses; the longest lasting response was 17 months.

Among all 57 evaluable patients in the interim analysis, the interim ORR was 44%, and the median duration of response (DOR) was 8.7 months vs 5.9 months with leucovorin calcium/folinic acid plus irinotecan and oxaliplatin (FOLFIRINOX) on its own as reported in other clinical studies. Moreover, the disease control rate (DCR) was 77%, which included stable disease among 33% of patients. Mitazalimab also produced a manageable safety profile when administered in combination with chemotherapy.

Investigators expect to share topline data from the OPTIMIZE-1 trial early in the first quarter of 2024.

“These second interim results from OPTIMIZE-1, in which mitazalimab again demonstrates a consistent response rate, together with the durable responses in several patients with extremely aggressive disease is particularly encouraging,” study investigator Jean-Luc Laethem, MD, PhD, a professor at Erasmus University Hospital, Brussels, said in the press release. “The consistent [ORR] together with the positive signal on [DOR]…gives us further crucial insight into the efficacy of mitazalimab and provides more evidence of the potential of this CD40 agonist to be further developed for becoming a therapeutic option for first-line patients [with PDAC].”

In the ongoing, open-label, multi-center phase 2 OPTIMIZE-1 study, previously untreated patients with metastatic PDAC received mitazalimab intravenously every 14 days plus modified FOLFIRINOX.

The study’s primary end points include ORR and incidence of dose-limiting toxicities. Secondary end points include overall survival, progression-free survival, anti-tumor activity based on RECIST v1.1 guidelines, and adverse effects.

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

Patients were unable to enroll on the study if they had other types of non-ductal tumors of the pancreas, other current cancer or history of cancer within 3 years of study entry, or known central nervous system metastases. Patients were also unsuitable for enrollment if they had any uncontrolled intercurrent illness, a history of myocardial infarction within 12 months of beginning study treatment, or received prior treatment with irinotecan or platinum-based chemotherapy.

The FDA previously granted orphan drug designation to mitazalimab as a treatment for patients with pancreatic cancer in May 2023.²

“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 a press release at the time mitazalimab received orphan drug designation.

References

1. Alligator Bioscience announces positive second interim efficacy analysis from mitazalimab OPTIMIZE-1 phase 2 study in 1st line pancreatic cancer. News release. Alligator Bioscience. June 26, 2023. Accessed June 27, 2023. https://rb.gy/09phr
2. 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