INVINCIBLE Study Demonstrates Tumor Necrosis and Immune Activation in Early Stage Breast Cancers

The Ottawa Hospital and Ontario Institute of Cancer Research ("OICR"), along with Intensity Therapeutics, Inc., will present updated data from the INVINCIBLE study at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting. INVICIBLE is a randomized, phase 2 presurgical window of opportunity trial for Intensity's intratumoral INT230-6 comprising SHAO (dispersion enhancer), vinblastine (VIN) and cisplatin (CIS), that is evaluating clinical and biological effects in patients with early-stage operable breast cancer.

"For a breast cancer patient, the typical waiting period of 2-6 weeks from diagnosis to surgery is a very anxious time. Surgeons and patients feel helpless, as there are currently no therapeutic options for the patient during this time," said Angel Arnaout, MD, Scientist and Surgical Oncologist at the Ottawa Hospital, and Professor of Surgery at the University of Ottawa and Co-lead of OICR's Window-of-Opportunity Network. "INT230-6 remains in the tumor following injection and can cause tumor cell death and high levels of necrosis in multiple breast cancer subtypes including triple negative breast cancer, as demonstrated by Part 1 of this study. Interestingly, we also saw immune activation with a relative increase in the abundance of CD4 T naïve, B and NK cells, post treatment, and, within the tumor microenvironment, a relative increase in abundance of CD8 memory T, CD4 naïve and B cells, post treatment, when comparing drug treated with control samples. The ability to use just one or two doses of this agent to elicit a rapid and marked cytotoxic and immune induction response within the tumor during the surgical waiting period, all without an increase in postoperative complications, is very novel and highly attractive to patients. We are excited about how this may shift the paradigm on how we treat cancer patients awaiting surgery, in general. We look forward to future studies to demonstrate how this intratumoral agent can have systemic benefit and long-term impact in patients with breast cancer."

The INVINCIBLE study enrolled 91 women with newly diagnosed, operable early-stage intermediate or high-grade T1-T2 invasive breast cancers 2 to 5 weeks prior to surgery (lumpectomy or mastectomy). Dose was set by the diameter of the tumor. Subjects were randomly allocated (2:1) prior to resection to  1 to 3 IT injections of INT230-6 versus no treatment (part 1 n=29) or saline sham injection (part 2 n=58). Part 1 evaluated safety, feasibility, and dose amounts. Part 2 was a double-blind, randomized arm. The objective of using saline will be to rule out the potential confounding effect of hydrostatic pressure on tumor necrosis. The results of Part 2 will further evaluate the potential cytotoxic, immunomodulatory and other biologic effects of INT230-6 and its role as a potential cancer therapy in breast cancer patients awaiting surgery. The INVINCIBLE study is being conducted under a Health Canada (HC) approved Clinical Trial Application (CTA), under the direction and supervision of Principal Investigator, Dr. Angel Arnaout. The Ottawa Hospital Research Institute conducted subject enrollment and treatment and will evaluate clinical responses. OICR will analyze subject immune responses and conduct biomarker analyses such as Ki67 and T-cell repertoire.

"INT230-6's ability to rapidly cause high levels of tumor necrosis combined with immune activation in early stage breast cancer patients with only low grade adverse events is unprecedented and quite exciting," said Lewis H Bender, president and chief executive officer of Intensity Therapeutics. "The results from the INVINCIBLE study, coupled with our data in metastatic patients, provide strong evidence and support for the potential of our drug in treating cancer patients from before surgery to late stage disease. We look forward to the full data set from the INVINCIBLE study and further development of our pioneering new medicine."