Intensity Therapeutics has published comprehensive phase 1/2 clinical trial results for its investigational intratumoral therapy INT230-6 in eBioMedicine, a Lancet Discovery Science journal, demonstrating promising efficacy and safety outcomes in patients with advanced metastatic cancers who had exhausted multiple treatment options.
The IT-01 study enrolled 64 heavily pretreated patients with over 20 different types of advanced solid tumors, including breast, sarcoma, pancreatic, lung, and head and neck cancers. These patients had progressed following a median of three prior lines of therapy and were not candidates for standard treatments.
Clinical Efficacy Results
The intratumoral injection therapy achieved a disease control rate of 75% (48/64 patients) and median overall survival of 11.9 months across the diverse patient population. According to the study authors, these results compare favorably to historical phase 1/2 studies that typically report median overall survival of 4 to 7 months in similar patient populations.
In a particularly notable subset, metastatic sarcoma patients receiving only INT230-6 achieved a median overall survival of 21.3 months. Additionally, 15 of 64 patients survived for more than 21 months overall.
Dose-Response Relationship
An exploratory analysis revealed significant differences based on treatment coverage. Patients receiving INT230-6 at doses treating greater than 40% of their total tumor burden demonstrated superior outcomes compared to those treated with less than 40% coverage:
- Disease control rate: 83.3% (40/48) versus 50% (8/16)
- Median overall survival: 18.7 months (95% CI: 11.5–23.5) versus 3.1 months (95% CI: 1.6–5.9)
- Hazard ratio: 0.17 (95% CI: 0.081–0.342); P<0.0001
The survival benefit remained consistent across a range of tumor burdens and sizes.
Immune Activation and Abscopal Effects
The study documented notable immune system engagement following INT230-6 treatment. In 13 of 14 matched pair biopsy slides, researchers observed increased activated CD4+ and CD8+ T cells infiltrating the tumor microenvironment.
Approximately 20% of patients in the >40% tumor burden treatment group experienced abscopal effects, where uninjected tumors shrank following local therapy administration. "Uninjected tumors shrinking from a locally administered therapy, referred to as abscopal effects, are generally rare for local therapies," noted Anthony El-Khoueiry, M.D., Associate Director for Clinical Research at USC Norris Comprehensive Cancer Center and the study's senior author.
Safety Profile
The therapy demonstrated a favorable safety profile with no dose-limiting toxicities reported among the 64 monotherapy patients. Only seven patients (10.9%) experienced grade 3 treatment-related adverse events, with no grade 4 or 5 events observed.
Pharmacokinetic analysis revealed that greater than 95% of the active cytotoxic agents remained within the injected tumors, with minimal systemic leakage even at doses as high as 175 mL administered to a single tumor.
Mechanism of Action
INT230-6 consists of two established anti-cancer agents, cisplatin and vinblastine sulfate, combined with a diffusion and cell penetration enhancer molecule called SHAO. This proprietary formulation, developed using Intensity's DfuseRx™ technology platform, enables the dispersion of cytotoxic drugs throughout tumors and facilitates their entry into cancer cells.
"The mechanism by which cancer is killed through the diffusion of cytotoxic agents following intratumoral injection of INT230-6 and systemic immune activation, as observed in preclinical models, translated well in the human setting," El-Khoueiry explained.
Clinical Development Program
Based on these results, Intensity Therapeutics has initiated several randomized controlled studies, including a Phase 3 trial in soft tissue sarcoma (NCT06263231) testing INT230-6 as second or third-line monotherapy compared to standard of care, with overall survival as the primary endpoint.
The company has also launched a Phase 2 study in collaboration with The Swiss Group for Clinical Cancer Research (NCT06358573) evaluating INT230-6 followed by standard immunochemotherapy versus standard treatment alone in patients with presurgical triple-negative breast cancer.
"We believe these are the first clinical results where a locally administered therapy used alone could potentially extend survival for patients with metastatic disease," said Lewis H. Bender, Founder, President, and CEO of Intensity Therapeutics.
