Alligator Bioscience achieved a significant milestone earlier this year when they met the primary endpoint of the Phase II OPTIMIZE-1 study. The study was designed to evaluate the CD40 agonist mitazalimab in combination with mFOLFIRINOX, the most effective chemotherapy for pancreatic cancer.
Alligator reaches proof-of-concept with mitazalimab
The study results showed a confirmed Objective Response Rate (ORR) of 40 percent and an unconfirmed ORR of 51 percent, indicating significant clinical benefit. In addition, a median Duration of Response (DoR) of 12,5 months, progression-free survival (PFS) of 7,7 months, a Disease Control Rate (DCR) of 79 percent in 57 evaluable patients and an Overall Survival (OS) of 14,3 months were reported.
Dr Zev Wainberg, associate director of the UCLA Gastrointestinal (GI) Oncology Program and clinical consultant for the mitazalimab clinical development program, highlighted the significance of the DoR in the OPTIMIZE-1 trial, noting that it exceeds previously reported duration of response values in metastatic pancreatic cancer. This prolonged response is expected to lead to improved overall survival. Data presented to date suggest even longer durations as the study progresses.
Important publication for Alligator
Alligator continues to attract great interest from the scientific community. This is particularly evident during ASCOmeeting in Chicago, where the company is presenting two clinical abstracts for its lead candidate.
Interest increased further after the OPTIMIZE-1 data were published in The Lancet OncologyAccording to Clarivate's Journal Citation Reports, the journal has an impact factor of 51,1, making it “the world-leading clinical research journal in oncology globally.”
Alligator CEO Soren Bregenholt is present at the ASCO conference, and according to him, the publication is generating a lot of attention.
- Presenting our clinical data at such a prestigious event like ASCO, and then publishing in a world-leading and peer-reviewed journal, is a significant milestone for Alligator Bioscience. There was substantial interest in our presentations at ASCO, and this impression was further reinforced by the strong feedback received in response to The Lancet Oncology article. It enhances our profile with these important audiences and is a validation of both the robustness of our research and the exciting potential of mitazalimab, on which we are expecting follow-up data from the OPTIMIZE-1 trial in late June.
The publication is expected to support Alligator in its pursuit of a commercial partnership for the late-stage clinical development of mitazalimab. A pivotal registration study is planned to begin in the first half of 2025.
Start of new phase I study with mitazalimab
Alligator Bioscience continues to advance its clinical program and interest in mitazalimab does not appear to be waning. Alligator has been approached by several clinical centers interested in conducting investigator-initiated studies. An example of this is the Phase Ia/b study of intratumoral mitazalimab in locally advanced pancreatic cancer (LAPC) that began at one center in May. The study is funded by National Cancer Institute and is carried out by Moores Cancer Center vid University of California San Diego and aims to evaluate the safety and efficacy of mitazalimab in surgical irreversible electroporation (IRE).
This technique uses short, intense electrical pulses to destroy cancer cells. It attacks the cells without damaging surrounding tissue, making it a good option for treating tumors near vital tissues. According to Rebekah White, MD, principal investigator of the study, preclinical data suggest that the combination of IRE and a CD40 agonist may lead to systemic antitumor effects.
CEO insights
BioStock contacted the CEO Soren Bregenholt to get his perspective on the company's latest successes.
Søren, how significant is this latest publication?
– It is very important, and we are naturally proud, to have this validation from the scientific community of the highly promising results of the OPTIMIZE-1 mitazalimab study – both from The Lancet Oncology and also our presentations at ASCO. A substantial number of patients were either on treatment or in the follow-up at the time of the primary analysis. Consequently, the 18-month survival follow-up data, which we expect at the end of June 2024, should provide further important insights into the potential of mitazalimab.
How will this impact your push towards phase III and ongoing partnering efforts?
- We are currently conducting due diligence and negotiations aimed at finding the best partner to take mitazalimab through Phase 3, regulatory approval and commercialization. This strong validation of, and publicity around, the data of course help to maintain the profile of mitazalimab, and Alligator Bioscience, with potential partners. It is also a good reminder of the approaching follow-up data.
Do you anticipate that the publication will have an impact on Alligator's standing and credibility in the field of oncology, including investors?
- Firstly, I would say that our track record, and the initial data release in January 2024, already provide us with a strong reputation as an innovative biotech company developing tumour-directed immunotherapies with the potential to significantly improve treatment options for cancer patients. We regularly receive strong feedback from both investors and scientists on the work we are doing, and the publication in The Lancet Oncology will further reinforce that.
Regarding the new phase I trial, why is IRE the basis for this phase I study with mitazalimab?
- Simplistically, the IRE procedure directs a localized high voltage current through the pancreatic tumor, which kills the tumor's cells. It is used for a number of solid tumors, and Dr. White's lab is pioneering its use in pancreatic cancer. In this trial she will test whether co-treatment with mitazalimab will activate the immune system to eradicate any residual tumor cells, which could potentially translate into a long-term survival benefit. As IRE is a localized surgical procedure, mitazalimab is administered intratumourally. This will impact mitazalimab's function, but limit systemic exposure and hence minimize potential side effects.
– The current study is exploratory in nature, and good results may establish a basis for eventually developing mitazalimab in combination with IRE and other surgical procedures, in adjuvant or neo-adjuvant settings.
Could you speak to how you use investigator initiated trials in the development of mitazalimab?
- Absolutely, this is a brilliant point. Since we published the first mitazalimab data from the phase 2 study we have received dozens of study proposals from renowned clinical investigators around the world. These suggestions include novel studies within pancreatic cancer, but the majority is in other indications like colorectal, renal, biliary tract, lung cancer and others.
- To me this reflects the uniqueness of mitazalimab's mechanism, as well as its efficacy and safety profile. We are carefully assessing each of these opportunities, with each representing a unique way to explore novel development opportunities for mitazalimab in collaboration with the world's leading clinical investigators, and expand the number of patients that will eventually benefit from mitazalimab.