INT230-6 is a formulation of cisplatin and vinblastine with an amphiphillic penetration enhancer to improve dispersion and diffusion into cancer cells. This is the first product designed for selective delivery into tumors with the potential to deliver high payload levels directly into cancer cells while sparing healthy cells. In colon 26 animal models, injection into a sentinel lesion led to tumor necrosis, recruitment of dendritic cells into the tumor and activation of CD4 and CD8 T-cells. Injected tumors experienced high rates of complete response (up to 80%). Importantly, untreated lesions distal to the injection site also responded. Efficacy was synergistic when combined with checkpoint inhibitors.
Initial cohort enrolled subjects with advanced solid tumors with superficial lesions amenable to local injection. INT230-6 was administered intratumorally at a ratio of 1ml for each 4 cubic cm of tumor volume, once each month for a total of 5 cycles. Both the maximal dose into one tumor and the total dose (over multiple lesions) could be escalated on repeat cycles if no DLTs. Patients were monitored for safety weekly. Pharmacokinetic(Pk) samples and peripheral blood were collected for flow cytometry and circulating cytokines. Subsequent cohorts of twice monthly injections into superficial tumors and monthly injection into deep tumors commenced after comprehensive review of safety data in superficial tumors.
Thirteen subjects were treated with either melanoma, SCC, ovarian, chordoma, cholangiocarcinoma or H&N into single or multiple lesions. Pk analysis revealed negligible amounts of reduced platinum and vinblastine in blood, suggesting retention in the tumor compartments. No DLTs or drug related SAEs were reported. The most frequent adverse event was grade 1 or 2 injection site pain, or other local symptom (infection or blister). Subjectively, some injected lesions were noted to change as soon as 1 week with flattening and areas of necrosis.
INT230-6 was safe when administered locally to tumors at doses given. Updated results will be presented including biomarker and response data. Additional cohorts including higher drug concentrations and combination with an anti-PD1 antibody.
Clinical trial identification
Legal entity responsible for the study
Ian B. Walters, MD.
A. El-Khoeuiry, L.L. Siu, N. Azad, A.J. Olszanski: Funding to institutions: Intensity Therapeutics. I.B. Walters: Employee and stockholder: Intensity Therapeutics. L. Bender: Founder and CEO of Intensity Therapeutics, named on the patents, stock holder and employee of the company which manufactures the product being studied. L. Kamen: Consultant and stock owner: Intensity therapeutics.