Announcement • Jul 15
Intensity Therapeutics Restarts Patient Treatment In The Randomized Presurgical Triple Negative Breast Cancer Phase 2 Clinical Trial INVINCIBLE-4 Study
Intensity Therapeutics, Inc. announced that new patients have been administered INT230-6 in the INVINCIBLE-4 Study in Switzerland. The trial (NCT06358573) analyzes INT230-6 given before administration of the standard-of-care neoadjuvant immuno-chemotherapy and the standard-of-care alone by using a 2-cohort design. The study evaluates the pathological complete response rates of the two cohorts relative to a null hypothesis, which is a pathological complete response rate of = 0.6. The success of each cohort in rejecting the null hypotheses will be evaluated. The INVINCIBLE-4 Study is a randomized open-label, multicenter study to determine the clinical activity, safety, and tolerability of INT230-6 in patients with early-stage, operable triple-negative breast cancer who undergo standard-of-care treatment and standard-of-care alone. The primary endpoint is pathological complete response in the primary tumor and affected lymph nodes. In the amended protocol, patients will be randomized to receive a regimen of one dose of INT230-6 followed by standard-of-care, which consists of pembrolizumab, anthracyclines, carboplatin, cyclophosphamide, and paclitaxel, or to standard-of-care alone. The INVINCIBLE-4 Study reopens following a pause in patient accrual to evaluate skin irritation issues seen in some patients. In March 2026, a protocol amendment was submitted to Swissmedic and the Swiss Ethics Committee to resume enrollment using a slightly lower drug-to-tumor volume ratio and a single injection of INT230-6. Prior to the pause, fourteen patients were treated, seven with the combination and seven received the standard-of-care alone. Patients receiving INT230-6 prior to the standard-of-care reported a favorable trend towards much fewer overall grade 3 or higher adverse events and immune-related adverse events compared to those patients receiving the standard-of-care alone. The INVINCIBLE-4 Study is expected to enroll an additional 47 patients in Switzerland and France. INT230-6, Intensity's lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity's proprietary DfuseRx technology platform. The drug consists of two proven, potent anti-cancer agents, cisplatin and vinblastine sulfate, and a diffusion and cell penetration enhancer molecule that non-covalently conjugates to the two payload drugs, facilitating the dispersion of potent cytotoxic drugs throughout tumors and allowing the active agents to diffuse into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 causes a release of a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy. Approximately 11-17% of breast cancers test negative for estrogen receptors, progesterone receptors, and excess human epidermal growth factor receptor 2 protein, qualifying them as triple negative. Most patients with local triple-negative breast cancer typically receive immune/chemotherapy before surgery. Since the publication of Keynote-522, standard neoadjuvant treatment for triple-negative breast cancer includes systemic chemotherapy (anthracyclines, cyclophosphamide, paclitaxel, carboplatin) and the anti-PD-1 monoclonal antibody pembrolizumab. Pathological complete response rates are only 63%, with rates generally lower in the larger-sized T2 to T4 tumors. The toxicity of the Keynote-522 regimen is high, with 80% of patients experiencing grade 3 or higher treatment-related adverse events, including treatment-related adverse events that lead to death in 0.5% of patients. Intensity has completed two clinical studies that enrolled over 200 patients using INT230-6: a Phase 1/2 dose escalation study in metastatic cancers including sarcomas (NCT03058289), and a Phase 2 randomized control clinical trial in locally advanced breast cancer (the INVINCIBLE-2 Study) (NCT04781725) in women without undergoing chemotherapy prior to their surgery. The Company initiated a Phase 3 trial in soft tissue sarcoma (the INVINCIBLE-3 Study) (NCT06263231), testing INT230-6 as second or third-line monotherapy compared to the standard-of-care with overall survival as an endpoint. Intensity also initiated a Phase 2 study in collaboration with the Swiss Cancer Institute (the INVINCIBLE-4 Study) (NCT06358573) as part of a Phase 2/3 program evaluating INT230-6 followed by the standard-of-care immunochemotherapy and the standard-of-care alone for patients with presurgical triple-negative breast cancer. Pathological complete response is the endpoint.
