Cancer patients are often given cancer drugs through a needle inserted into a vein, a delivery method known as intravenous infusion, which delivers the drugs directly into the bloodstream. The goal is to achieve systemic blood levels of the drug that would kill visible tumors as well as any unseen circulating cancer cells that have spread to other parts of the body (micrometastases).
Unfortunately, administering drugs intravenously typically delivers only a low concentration of the drug to the actual tumor site. This approach, especially for late-stage cancers, is not particularly effective and can often be toxic to the patient. Consequently, there have been attempts at injecting cancer treatments such as chemotherapeutic drugs directly into the tumor. This approach, called intratumoral injection, has so far not been successful either in treating the injected tumor, the non-injected tumors, or micrometastases, possibly because of the drug’s difficulties with penetrating and dispersing into the cancer cells.
A new experimental drug, named INT230-6 by Intensity Therapeutics, is showing promise as a potential solution to this problem. INT230-6 is made up of two proven FDA-approved anti-cancer agents, cisplatin and vinblastine, which are typically administered intravenously during chemotherapy. What makes INT230-6 unique is the third agent that it contains — a novel penetration enhancer that helps rapidly disperse cisplatin and vinblastine throughout a tumor for better diffusion into cancer cells. UMass was selected as one of only a few sites around North America offering a phase I/II clinical trial involving intratumoral injection of INT230-6, which is in progress and currently recruiting participants. Giles Whalen, MD, a surgical oncologist and member of the UMass Cancer Center, is leading the trial at UMass as one of the principal investigators.
Dr. Whalen’s role as a principal investigator in this phase I/II trial stems from his previous work on cancer treatments involving intratumoral injection. Over the past decade, he explored an immunotherapy approach for melanoma that exploits the most abundant natural antibody in human blood (anti-α-Gal antibody) to destroy tumors. In these studies, a type of fat-soluble substance — known as α-gal glycolipid — that activates this antibody was injected directly into melanoma lesions of mice, resulting in an anti-tumor immune response, where there was regression of the injected tumor and prevention of tumor growth in distant sites. Dr. Whalen went on to conduct a phase I study to show that this approach is feasible and safe for use as an immunotherapy in melanoma patients. The approach, using a synthetic version of α-gal glycolipid, is now in further testing by a biopharmaceutical company.
Like the injection of α-gal glycolipid into tumors, the injection of INT230-6 into tumors also produces an anti-tumor immune response. But because of the new penetration enhancer that INT230-6 contains, it is able to permeate and kill the injected tumors, including large tumors, as shown in animal studies. INT230-6 also induces an immune response mediated by T-cells that targets both the tumors that were injected and those that were not injected, as well as micrometastases. These results hold promise for human cancer patients because, essentially, the animals in these studies are provided with immunity against the cancer. In the phase I/II trial at UMass, INT230-6 is being tested in patients with several types of refractory cancers including those at the surface of the skin (breast, squamous cell, head and neck) and tumors within the body such as pancreatic, colon, liver, and lung tumors. Multiple, escalating doses of INT230-6 will be tested. The clinical trial will also assess how INT230-6 works when it is combined with immunotherapy agents such as antibodies that target proteins on cells of the immune system (specifically, anti-PD-1 and anti-CTLA-4 antibodies).
The information obtained from this clinical trial will help determine the safety and tolerability, and the potential effectiveness, of dosing INT230-6 directly into several different types of cancers, with the ultimate goal of achieving tumor regression and improving the outcomes of cancer patients.
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