Intensity’s ongoing Phase 1/2 clinical study evaluates the intratumoral administration of escalating doses of INT230-6. We are evaluating INT230-6 in patients with several types of refractory superficial and deep solid tumors, including chordoma, melanoma, head and neck, lymphoma, breast, pancreatic, colon, liver and lung. There are several cohorts of subjects in the escalation portion of the protocol. Escalation is being by increased by dose amount, dose frequency and loading per tumor. (INT230-6 dose for a given tumor is is set by the calculated volume of the tumor as determined from imaging – not the patient’s body surface area.) There is also intrapatient escalation, meaning patients can receive increasing doses over the course of their 5 dose treatment depending on safety and tolerability. Three cohorts have been completed including dosing once per month and dosing with a tumor load of 1 mL of drug for every 4 cubic centimenters of tumor volume (1:4 ratio). Currently treatment is every two weeks at a 1:2 ratio. To date, our study steering committee has determined that there has been acceptable safety in treating both superficial and deep tumors. The study is on-going. A cohort is planned for combination of INT230-6 with anti-PD-1 agent, a well-known checkpoint inhibitor.
The primary study objective is to assess the safety and tolerability of single and multiple intratumoral doses of INT230-6 in subjects with advanced or recurrent malignancies. This will be assessed by the rate of ≥ grade 3 adverse events (AEs) attributed to INT230-6 and not the underlying disease. All recorded AEs will be listed and tabulated by system organ class, preferred term, and dose and coded according to the most current version of MedDRA. The incidence of AEs will be tabulated and reviewed for potential significance and clinical importance. AEs will be summarized for all reported data and by study period: a) up to and including 28 days post last dose of initial treatment, and b) from first dose of re-initiation of treatment, for subjects who re-initiate study therapy while in follow-up, up to 28 days post-dose of the last re-treatment dose. There are a number of secondary outcome measures, including a determination of preliminary efficacy that will be measured by control or regression of injected tumors by measurement of length, width and height (in centimeters) radio-graphically.
We also intend to determine pharmacokinetic parameters of each of the three main components of INT230-6 after single and then multiple IT tumor site injections. The study is also collecting blood, genetic and tissue to identify biomarkers and evaluate immune activity.