Intensity Therapeutics has published data for its experimental intratumoral therapy, INT230-6, which has shown significant survival benefits and disease control in patients with advanced, metastatic, or refractory cancers. 

The Phase I/II clinical trial (NCT03058289) evaluated the safety and efficacy of the novel drug in heavily pretreated patients across more than 20 cancer types. The findings published in the eBioMedicine journal highlight the potential of local tumor injection to not only destroy injected tumors but also activate a systemic immune response against uninjected metastases.

Following the release of the results, Intensity’s stock was up by 394% at market close on 30 October, compared to the market close on the previous day. The stock dropped 30% on Friday after the company announced a $4 million registered direct offering of common stock priced at $0.80 per share, significantly lower than its previous closing price. The company’s stock has taken a further tumble and is currently trading at $0.58.

Clinical Trial Results

The Phase I/II IT-01 trial enrolled 64 patients with advanced solid tumors who had progressed after a median of three prior lines of therapy. Key results from the study include:

• A disease control rate of 75% (48 out of 64 patients), indicating tumor shrinkage or stable disease.
• A median overall survival of 11.9 months, which compares favorably to the historically reported 4 to 7 months in similar early-phase trials for refractory cancers.
• In a subset of patients with metastatic sarcoma treated with INT230-6 alone, median overall survival reached 21.3 months.

A particularly striking finding emerged when researchers analyzed outcomes based on the proportion of a patient’s total tumor burden treated with the drug. Patients who received INT230-6 doses, treating more than 40% of their total tumor volume, saw:

• A disease control rate of 83.3%, compared to 50% in those treated with less than 40%.
• A median overall survival of 18.7 months, versus just 3.1 months in the lower-dose group.
• A hazard ratio of 0.17, indicating an 83% reduction in the risk of death.

One of the most notable observations was the occurrence of abscopal effects—the shrinkage of uninjected, distant tumors—in approximately 20% of patients who received higher drug volumes relative to their tumor burden. This suggests that local treatment with INT230-6 can stimulate a systemic immune response against cancer.

Biopsy analyses supported this finding. In 13 of 14 matched pair samples, researchers observed a notable increase in activated CD4+ and CD8+ T-cells within the tumor microenvironment after INT230-6 treatment. This immune infiltration is a key indicator that the therapy is engaging the immune system to fight cancer.

Favorable Safety and Pharmacokinetic Profile

INT230-6 demonstrated a favorable safety profile in the trial. Among the 64 monotherapy patients, no dose-limiting toxicities were reported. Only seven patients (10.9%) experienced Grade 3 treatment-related adverse events, with no Grade 4 or 5 events.

Pharmacokinetic data showed that over 95% of the cytotoxic agents (cisplatin and vinblastine) remained within the injected tumor, even with doses as high as 175 mL administered to a single tumor. This localized effect could help explain the drug’s low systemic toxicity.

“INT230-6 is a local treatment that kills cancer using a diffusion process following direct injection into tumors,” said Dr. Jacob Stephen Thomas of USC’s Norris Comprehensive Cancer Center, the paper’s first author. “The disease control rates and median survival compare favorably to those historically seen for such a diverse set of refractory cancer types.”

Dr. Anthony El-Khoueiry, senior author, emphasized the translational significance: “The abscopal effects and immune cell infiltration observed in this study highlight this intratumoral therapy’s potential to drive both a local and systemic anti-cancer activity.”

Future Development

Based on these results, Intensity Therapeutics has advanced INT230-6 into later-stage trials, including a Phase III INVINCIBLE-3 study (NCT06263231) in soft tissue sarcoma, testing INT230-6 as monotherapy against the standard of care. A Phase II/III INVINCIBLE-4 study (NCT06358573) in triple-negative breast cancer is also underway, which is evaluating INT230-6 in combination with immunochemotherapy.