Metastatic Melanoma Immunotherapy Shows Promise in Mice Study

Metastatic Melanoma Immunotherapy Shows Promise in Mice Study

Memgen LLC, a company that develops cancer immunotherapies, presented positive preclinical data for its main immuno-oncology drug, ISF35, during the 30th annual meeting of the Society of Immunotherapy of Cancer (SITC), held recently in National Harbor, Maryland.

ISF35 is a T cell cancer immunotherapy that promotes an anti-tumor immune response and can be used in combination with checkpoint inhibitors as a potential treatment for a broad range of cancers, including lung, metastatic melanoma, and hepatocellular carcinoma.

In the poster titled “Induction of Potent Systemic Anti-Melanoma Immunity through Intratumoral CD40 Activation and Checkpoint Blockade,” the company presented results from trials in mice models of B16 melanomas that were treated intra-tumorally with a replication defective adenovirus encoding ISF35. Other results, including the evaluation of  ISF35 treatment in combination with anti-PD-1 and anti-CTLA-4 blocking antibodies, were also presented.

The study, led by Willem Overwijk, PhD, and Manisha Singh, PhD, of The University of Texas MD Anderson Cancer Center, demonstrated that ISF35 caused CD8 T cell-targeted anti-tumor immunity in both injected and distal non-injected tumors in the mice, leading to inhibition and regression of tumor growth. Moreover, ISF35 in combination with anti-PD-1 was able to amplify CD8 T cell numbers within the melanoma microenvironment. Treating mice with a triple combination therapy of ISF35, anti-PD-1 and anti-CTLA-4 further improved efficacy and led to a complete regression of melanoma tumors in nearly 50% of the mice, while aiding in the production of memory CD8 T cells. “There have been significant advances in the survival and treatment of many cancer types with immune-oncology (IO) drugs, primarily as monotherapy with checkpoint inhibitors,” Mark Cantwell, PhD, Memgen president and co-inventor of ISF35, said in a press release.

The company is already planning to evaluate ISF35 in combination with Keytruda (pembrolizumab) in a phase I/II study in refractory metastatic melanoma.

“With the next wave of clinical development aiming to find the right combinations of IO drugs that improve patient outcomes while still keeping a tolerable safety profile, the preclinical results provide strong support that ISF35 in combination with checkpoint inhibitors can achieve this goal,” Dr. Cantwell said. “We look forward to soon beginning a phase I/II clinical trial of ISF35 and Keytruda (pembrolizumab) in refractory metastatic melanoma.  This trial will be an important step in identifying synergistic combinations that will enhance checkpoint immunotherapies.”

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