Background: INT230-6 is comprised of cisplatin (CIS), vinblastine (VIN) and an amphiphilic penetration enhancer which facilitates dispersion throughout tumors and diffusion into cancer cells. In preclinical experiments, INT230-6 led to necrosis and recruitment of immune cells with high rates of complete responses of injected and bystander tumors. This abstract highlights the safety and early pharmacodynamic activity of this approach. Methods: Patients with solid tumors that progressed on all standard treatments were enrolled. Dose escalation occurred by increasing number of tumors injected, loading per tumor, and total dose. INT230-6 was injected once every 2 weeks in multiple lesions for 5 sessions. Patients were monitored for safety and tolerability weekly. Pharmacokinetic(Pk) samples and peripheral blood were collected for flow cytometry and circulating cytokines. Pre and on study biopsies are ongoing. Results: 28 patients (14 unique cancer types) receiving a median of 3 prior treatments were enrolled. Doses from 0.3 ml up to-80 ml of INT230-6 were given into single lesions with some patients receiving a total of 120 mL ( = 9.7mg VIN exceeding the IV VIN dose) without significant systemic absorption or typical cytotoxic adverse events. Pk analysis suggests that systemic exposure of VIN or CIS is ~10% of injected. No DLT’s or drug-related SAE’s reported. The most frequent adverse event was grade 1 or 2 pain at injected site. Superficial tumors showed signs of response including flattening, areas of necrosis and ulceration. Tumor reduction, apparent in in both injected and bystander tumors, may indicate an abscopal effect. An increase > 30% in CD8 T-cells was seen in the blood of 3/9 evaluable patients. Conclusions: INT230-6 was safe and well tolerated in > 100 injections (28 patients) with encouraging activity and pharmacodynamic effects in advanced refractory tumors. Additional analysis of immune cells from on study biopsies will be presented. A new cohort will evaluate combination with an anti-PD1 antibody to understand if local tumor destruction can increase systemic antigen load, increase immune cell recognition and initiate a systemic immune response. Clinical trial information: NCT 03058289.