Intensity Therapeutics has achieved a significant milestone by dosing the first US patient in its global Phase 3 INVINCIBLE-3 trial evaluating INT230-6 for metastatic soft tissue sarcoma. The randomized superiority study represents a potential breakthrough for patients with this deadly cancer, where median overall survival following second- and third-line treatments ranges between 10 and 15 months.
Trial Design and Patient Population
The INVINCIBLE-3 study (NCT06263231) is designed to enroll approximately 333 patients across eight countries, with regulatory documents already filed to initiate the trial in Canada and Europe. The study employs a 2:1 randomization ratio, where two patients receive INT230-6 for every one patient receiving investigator's choice of standard-of-care systemic chemotherapy.
Eligible patients must be 18 years or older with histologically proven, unresectable, locally advanced, or metastatic soft tissue sarcoma. Key inclusion criteria include measurable disease per RECIST 1.1 criteria, at least one target tumor suitable for injection measuring ≥2 cm by CT or MRI, ECOG performance status of 0-2, and progression following anthracycline-based or alternative standard therapies. The study focuses on three sarcoma subtypes: leiomyosarcoma, liposarcoma, and undifferentiated pleomorphic sarcoma.
Promising Preclinical Data
The Phase 3 initiation follows encouraging results from Intensity's Phase 1/2 dose escalation study. In a heavily pretreated sarcoma population that had progressed following a median of three lines of therapy, INT230-6 demonstrated a median overall survival of 21.3 months as monotherapy. This represents a substantial improvement over the 10-15 month median survival typically seen with current standard treatments in this setting.
"During our phase 1/2 metastatic dose escalation study, in a sarcoma population that had progressed following a median of 3 lines of therapy, we reported a median overall survival of 21.3 months with our drug alone," said Lewis H. Bender, Intensity Therapeutics' founder, chairman, and chief executive officer.
Novel Mechanism of Action
INT230-6 represents a unique approach to cancer treatment, designed for direct intratumoral injection using Intensity's proprietary DfuseRx™ technology platform. The investigational drug comprises two proven anti-cancer agents—cisplatin and vinblastine—combined with a penetration enhancer molecule (SHAO) that helps disperse the cytotoxic drugs throughout tumors for diffusion into cancer cells.
The drug's design ensures that all three agents remain within the tumor, resulting in a favorable safety profile. Beyond direct tumor killing, INT230-6 releases a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects without the immunosuppression often associated with systemic chemotherapy.
Addressing Unmet Medical Need
Soft tissue sarcoma represents a significant unmet medical need, with approximately 197,000 patients living with sarcoma in the United States. The disease primarily affects soft tissues such as muscle, fat, blood vessels, nerves, tendons, and joint linings, most commonly occurring in the arms, legs, and abdomen. Using the US SEER database, Intensity estimates that 14,337 patients have regional or distant metastatic disease involving the three sarcoma subtypes included in the study.
"Patients, their caregivers, and physicians worldwide desperately need improved treatment options and we are excited to have finally begun testing our new approach in Phase 3," Bender emphasized, highlighting the critical need for new therapeutic approaches in this challenging cancer type.
The INVINCIBLE-3 trial is expected to complete by December 2028, with overall survival as the primary endpoint. The study's success could potentially establish INT230-6 as a new standard of care for patients with metastatic soft tissue sarcoma, offering hope for improved outcomes in a disease with historically poor prognosis.
