The clinical drug candidate mitazalimab (previously ADC-1013) is an agonistic—or stimulatory—antibody that targets CD40, a receptor on the dendritic cells of the immune system, which are the cells that detect enemies such as cancer cells. Mitazalimab’s activation of CD40 enables dendritic cells to stimulate the immune response’s weapons more effectively—in this case, T cells—allowing the immune system to selectively attack the cancer. Mitazalimab has been optimized using Alligator’s unique FIND technology, with the aim of improving binding affinity. This makes it possible to achieve efficacy with very low doses. In preclinical experimental models, mitazalimab has been shown to induce a potent tumor-targeted immune response and provide long-lasting tumor immunity. In addition, preclinical data have demonstrated how mitazalimab can be used against multiple types of cancer.
To date, the clinical program has comprised two Phase 1 studies.
The first study was conducted by Alligator with a focus on intratumoral administration. The results showed that clinically relevant doses of mitazalimab are well-tolerated.
Further promising safety and tolerability data from a second Phase 1 clinical study with mitazalimab in cancer patients was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2019. The results showed that the adverse effects were mostly mild and transient. The study comprised a total of 95 patients. Doses of up to 1200 μg/kg i.v. with no premedication of corticosteroids, and up to 2000 μg/kg with corticosteroids proved safe and tolerable. The results also gave signs of clinical activity. Partial response was observed in one renal cancer patient, while 10 patients showed disease stability for at least six months.
The Phase 2 clinical trial application (CTA) was approved in March, 2021. The study OPTIMIZE-1 is an open-label, multi-center trial assessing the clinical efficacy of mitazalimab in combination with chemotherapy (mFOLFIRINOX) in patients with metastatic pancreatic cancer. The OPTIMIZE-1 study has been initiated with first patient dosed in Q3, 2021. The study will be performed at several clinics in Europe.
On January 2, 2023, Alligator announced strong interim results from the ongoing OPTIMIZE-1 study. The results demonstrated an objective response rate (ORR) of 52% in 23 evaluable patients, as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Disease control rate, the proportion of patients with objective response or stabilization of disease, was more than 90%. These data are noteworthy, especially in the light of an ORR of 31.6% reported with FOLFIRINOX in a similar patient population. This data was later discussed in March with the principal investigator of the OPTIMIZE-1 study, Jean-Luc van Laethem, together with Alligator CMO Sumeet Ambarkhane, and was presented at the ASCO Annual Meeting in Chicago, in June 2023. The patient recruitment in OPTIMIZE-1 was announced completed on April 12, 2023 and in May, Alligator received an FDA Orphan Drug Designation for mitazalimab in pancreatic cancer.
On June 26, Alligator announced additional positive interim phase 2 data from the OPTIMIZE-1 study, where the follow-up on the initial futility cohort showed deepening of tumor responses and an increase in Objective Response Rate to 57%. More than half of the responders showed maintained responses beyond 10 months, the longest being 17 months. The Duration of Response in the entire cohort was 8.7 months well above what has been reported for chemotherapy alone in similar patient populations, while the Objective Response Rate in the full cohort after two to 17 months of treatment was 44%.
Based on these positive results, Alligator plans to initiate discussions with regulators in the US and Europe on potential accelerated development and approval pathway for mitazalimab in pancreatic cancer, while continuing patient enrolment in this ongoing trial. Top-line data from this trial are expected in Q1 2024.
In April 2023, Alligator Bioscience announced that the FDA had authorized to initiate a second Phase 2 trial with mitazalimab in urothelial carcinoma. The Company expects the OPTIMIZE-2 study to begin in H1 2024, or earlier, subject to operational feasibility.