Intensity Therapeutics, Inc. and The Swiss Group for Clinical Cancer Research (SAKK) have announced the dosing of the first patient in the INVINCIBLE-4 Study, a Phase 2 clinical trial evaluating INT230-6 in patients with localized triple-negative breast cancer (TNBC). The trial, known as SAKK 66/22, is designed to assess the efficacy and safety of INT230-6 when administered in combination with standard-of-care (SOC) neoadjuvant immuno-chemotherapy compared to SOC alone.
The INVINCIBLE-4 Study (NCT06358573) is a randomized, open-label, multicenter trial expected to enroll approximately 54 patients across Switzerland and France. Patients will be randomized 1:1 to receive either two doses of INT230-6 followed by SOC, consisting of pembrolizumab, anthracyclines, carboplatin, cyclophosphamide, and paclitaxel, or SOC alone. The primary endpoint is the pathological complete response (pCR) rate in the primary tumor and affected lymph nodes.
Rationale for INT230-6 in TNBC
Triple-negative breast cancer, representing 11-17% of all breast cancers, is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) overexpression. This subtype is often more aggressive and associated with poorer prognosis due to limited targeted treatment options. The current standard neoadjuvant treatment includes systemic chemotherapy and pembrolizumab; however, pCR rates remain suboptimal, particularly in larger tumors, with significant associated toxicities.
INT230-6: Mechanism of Action
INT230-6 is an investigational product designed for direct intratumoral injection, comprising cisplatin and vinblastine, along with a penetration enhancer molecule (SHAO). This combination aims to facilitate the diffusion of cytotoxic drugs throughout the tumor, inducing local immunogenic cell death without systemic chemotoxicity. Preclinical data suggest that INT230-6 can release tumor-specific neoantigens, promoting immune system engagement and systemic anti-tumor effects without immunosuppression.
Expert Commentary
Andreas Mueller, M.D., Past-President of the Breast Cancer Group at the National Swiss Association for Clinical Cancer Research, stated, "Many TNBC patients undergoing SOC treatment alone fail to achieve a pathological complete response at the time of surgery, especially in larger tumor sizes. INT230-6 has the potential to fill this unmet need... through its anti-cancer mechanisms of action that cause tumor cell necrosis and ignite an anti-cancer immune-based response."
Ursina Zuerer-Haerdi, MD, Lead Physician for the Department of Medical Oncology and Hematology at the Cantonal Hospital in Winterthur, Switzerland, added, "We have worked with Intensity to design a study for this novel intratumoral agent with the potential to increase the pathological complete response rates of the current best standard of care that would be clinically meaningful."
Markus Joerger, Prof. MD-PhD and Coordinating Investigator on the study, noted, "INT230-6 tackles the innate immune pathway that is not addressed by immune checkpoint inhibitors, and it is suggested to complement the systemic neoadjuvant backbone... We believe that the SAKK 66/22 study will provide crucial data to inform a large randomized clinical trial in patients with early-stage TNBC."
Looking Ahead
The INVINCIBLE-4 Study seeks to determine if the addition of INT230-6 to standard neoadjuvant chemotherapy can improve pathological complete response rates in patients with localized triple-negative breast cancer. The results of this trial could potentially offer a new treatment strategy for this aggressive form of breast cancer.
