Mitazalimab, a human CD40 agonistic IgG1 antibody, works by reducing immune suppression, sensitizing tumors to chemotherapy, and inducing long-lasting anti-tumor T-cell responses. The OPTIMIZE-1 (NCT04888312) Phase Ib/II trial is an open-label; multicenter study evaluating the safety and efficacy of mitazalimab combined with mFFX in chemotherapy-naive metastatic pancreatic ductal adenocarcinoma (mPDAC) patients.

Alligator Bioscience announced positive top-line results from the OPTIMIZE-1 Phase II trial in pancreatic cancer, revealing that mitazalimab combined with mFOLFIRINOX achieved a 40.4% overall response rate (ORR), a median duration of response (DoR) of 12.5 months, and a median overall survival (mOS) of 14.3 months. This compares favorably to the 11.1 months mOS seen with first-line chemotherapies FOLFIRINOX and NALIFIROX. With more than half of the patients still in the study at the primary analysis, the 18-month survival follow-up data was presented at ASCO 2024.

Discussions with the US Food and Drug Administration (FDA) have established a clear pathway for the development and approval of mitazalimab in pancreatic cancer. Based on emerging data from the OPTIMIZE-1 study, the FDA has provided additional guidance on dose characterization and endorsed OPTIMIZE-1 as a Phase III-enabling study. Consequently, mitazalimab is set to proceed directly to a global Phase III registration study, which Alligator is preparing to initiate in the first half of 2025 in collaboration with a commercial partner. Additionally, in line with the FDA's advice, Alligator has begun enrolling 15 additional patients at a 450 µg/kg dose as part of their Phase III preparation.

KOL insights

“The median DoR in the OPTIMIZE-1 study appears more than two times better, translating in better overall survival for these patients. So, the fact that there are still 51 percent of the patients ongoing in the study, and 32 percent of patients still on treatment, would suggest that we are going to end up seeing quite a bit longer duration of response and survival as the data matures.”–Expert Opinion.

“We are pleased with the signs of clinical activity observed in the OPTIMIZE-1 analysis and believe that mitazalimab in combination with chemotherapy warrants continued development for the treatment of pancreatic cancer patients, which is an area of high unmet need.”–Expert Opinion.

Conclusion

As per Delveinsight’s estimates, there were approximately 60,000 incident cases of Pancreatic Cancer in the United States in 2023. Having achieved the primary endpoint in its OPTIMIZE-1 Phase II trial for pancreatic cancer, Alligator Bioscience is set to begin preparations for a Phase III trial anticipated to start in early 2025. The combination of mitazalimab with mFFX has proven to be a feasible regimen with a manageable safety profile. Enhanced efficacy was observed particularly in patients with KRAS G12V and R mutations. The promising duration of response and associated survival benefits in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC) support the continued development of mitazalimab in a confirmatory Phase III study.