Background: Sarcomas are a rare and diverse group of solid tumors from mesenchymal cells; chemotherapy provides limited benefit for metastatic disease. INT230-6 is a novel formulation of cisplatin (CIS), vinblastine (VIN) and a tissue dispersion enhancer (SHAO) designed for intratumoral (IT) delivery. The drug diffuses into cancer cells, causes apoptosis and recruits dendritic and T-cells to the tumor. Adding ipilimumab (IPI) appears to improve INT230-6 responses in models and clinically. The study evaluated INT230-6 for safety and efficacy alone and with intravenous (IV) IPI. Previously reported results showed INT230-6 alone induced tumor regression, T-cell influx and abscopal effects in uninjected lesions^1,2. Methods: IT-01 is an open-label phase1/2 study in adults with locally advanced, unresectable or metastatic solid tumors, including sarcoma. INT230-6 dose was set by tumor diameter or volume. INT230-6 was dosed IT Q2W for up to 5 doses alone or with IPI at 3mg/kg Q3 weeks for 4 doses. Maintenance INT230-6 dosing was Q9W. Results: The study enrolled 29 sarcoma patients with 11 subtypes (mainly leiomyosarcoma, liposarcoma, pleomorphic, chondrosarcoma and chordoma). The maximum INT230-6 dose at a single visit was 175 mL (87.5 mg of CIS, 17.5 mg VIN) in 1 or more tumors, an amount that exceeds an IV dose of VIN or CIS. PK analysis shows that >95% of VIN stays in the tumor. The >20% treatment-related adverse events (TRAEs) in evaluable monotherapy patients (n=15) were localized pain (80%), nausea (40%), fatigue (33%), decreased appetite (27%), and vomiting (20%). The >20% TRAEs in evaluable IPI/INT230-6 patients (n=14) were fatigue (39%), localized pain (39%), nausea (31%), pruritus (23%), rash (23%) and vomiting. G3 TRAEs occurred in 20% and 7% of patients in the INT230-6 and combination arms respectively with no grade 4 or 5 events in either arm. RECIST metrics are confounded by IT injections due to the large volume of highly retained INT230-6 and the influx of immune infiltrates. Analysis of median overall survival (mOS) for INT230-6 alone (n=15) was 649 days. For INT230-6 dosed at a volume/total tumor burden (TTB) ratio of ≥40%, the mOS was 715 days. The mOS of the combination has not been reached with over 1 year of median follow-up. OS data compare favorably to a synthetic control (mOS of 205 days) based on historical data³. The hazard ratios of INT230-6 alone or with IPI for OS to the synthetic control were 0.446 and 0.270, p-values <0.01. Conclusions: INT230-6 dosed IT alone or with IPI was well-tolerated in diverse sarcomas. INT230-6 use was associated with immune infiltration and favorable mOS as compared to a synthetic control, particularly when ≥40% of the TTB was injected. A randomized phase 3 trial vs. SOC in selected sarcoma subtypes with an OS endpoint is planned. References: 1. Oncoimmunology. 2019 Jul 16;8(10). 2. ASCO 6/2022. 3. Sci Rep. 2016;6:35448. Clinical trial information: NCT03058289.