お知らせ • Mar 13
Intensity Therapeutics, Inc. Provides Update on Phase 2 Presurgical Triple-Negative Breast Cancer Invincible-4 Study
Intensity Therapeutics, Inc. provided an update on the INVINCIBLE-4 Study. Preliminary observations of the INVINCIBLE-4 Study to date showed that five (5) out of seven (7) patients (71.4%) who received INT230-6 prior to standard of care ("SOC") ("Cohort A") achieved a pathological complete response ("pCR") whereas two (2) out of six (6) (33%) patients in the SOC arm alone ("Cohort B") achieved a pCR, with one patient still to be evaluated. (44%) fewer grade 3 or higher Adverse Events ("AEs") were observed in Cohort A compared to Cohort B. A protocol amendment has been submitted to the Swiss Agency for Therapeutic Products ("Swissmedic"), Switzerland's regulatory authority, and the Swiss Ethics Committee to resume enrollment. In September 2025, enrollment was paused by the Company due to skin irritations observed in Cohort A. In early March 2026, a protocol amendment was submitted to Swissmedic and the Swiss Ethics Committee to resume enrollment using a lower drug volume per tumor volume ratio and a single injection of INT230-6. The SOC in the INVINCIBLE-4 Study is the Keynote-522 study regimen, a 6-month presurgical treatment consisting of pembrolizumab every three weeks, then paclitaxel, followed by carboplatin and 4 doxorubicin or epirubicin with cyclophosphamide. The INVINCIBLE-4 Study enrollment criteria is limited to patients with tumors sizes = 1.5 cm, whereas the Keynote-522 study enrolled tumors > 1.0 cm. As a result, patients in the INVINCIBLE-4 Study, on average, have larger tumors than patients in the Keynote-522 study. Patients undergo the Keynote-522 regimen in an attempt to obtain a pCR, which has been shown to significantly reduce the risk of disease recurrence. pCR is an endpoint that the U.S Food and Drug Administration ("FDA") and the European Medicines Agency could allow for an accelerated or conditional marketing approval. Overall, fourteen (14) patients have been treated to date in the INVINCIBLE-4 Study, with seven (7) in each cohort. The expected total enrollment is up to sixty-one (61) patients. Preliminary observations for the fourteen patients treated to date are as follows: Cohort A: A pCR was achieved in five (5) out of seven (7) patients (71.4%) who received injections of INT230-6 prior to SOC. Six (6) patients received two (2) injections and one patient, who achieved a pCR, received one (1) injection. Cohort B: A pCR was achieved in two (2) out of six (6) patients (33%) who received the SOC alone, with one patient still to be evaluated. The pCR analysis is ongoing, and results are preliminary and early. Safety Data Observations (through March 2, 2026): Cohort A: There has been a total of fourteen (14) grade 3 or higher AEs, only one (1) of which is considered a common immune-related side effect of checkpoint immunotherapy. Cohort B: There has been a total of twenty-five (25) SOC-related grade 3 AEs, of which four (4) are considered common or rare side effects of immune checkpoint inhibitors (three grade 3 and one grade 4). The safety data for patients who received INT230-6 plus SOC remain favorable compared with SOC alone. In the Company's first presurgical Breast Cancer study completed in 2023 (the "INVINCIBLE-2 Study"), fifty-eight (58) women received one (1) to three (3) injections of only INT230-6. Additionally, skin issues were rare, and surgery was performed without complications. The Company expects presentation of more detailed results for the seven (7) Cohort A patients at a future oncology conference. About Triple Negative Breast Cancer in the Presurgical Setting: Women with aggressive forms of breast cancer, such as Triple Negative Breast Cancer (TNBC), are often counseled to undergo pre-surgical (neoadjuvant) systemic therapy in advance to reduce the risk of the disease returning. Having a pathological complete response, meaning the absence of live cancer at the time of surgery, has been shown to result in a lower risk of disease recurrence from 50% to 16% at 5 years. Approximately 11 to 17% of breast cancers test negative for estrogen receptors ("ER"), progesterone receptors (PR), and overexpression of human epidermal growth factor receptor 2 ("HER2") protein, qualifying them as triple negative. There are approximately 56,000 new cases of TNBC in the US and 420,000 worldwide diagnosed each year, 85% of which are local to the breast. TNBC is considered to be more aggressive and has a poorer prognosis than other types of breast cancer, because there are fewer available targeted medicines. Most patients with local TNBC typically receive immunochemotherapy before surgery. Since the publication of Keynote-522, the standard neoadjuvant treatment for TNBC includes systemic chemotherapy (anthracyclines, cyclophosphamide, paclitaxel, carboplatin) and the anti-PD-1 monoclonal antibody pembrolizumab. pCR rates range from 50 to 65%, depending on tumor size. Rates are generally lower in the larger-sized tumors or with lymph node metastasis. The toxicity of the Keynote-522 regimen is high, with 77% of patients experiencing grade 3 or higher treatment-related AEs, including treatment-related adverse events that lead to death in 0.5% of patients. About a Potential INT230-6 Approval Pathway in the Presurgical Setting: The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint. pCR is an accepted FDA accelerated approval criterion for approval in high-risk breast cancer, such as TNBC subtype. Pathological complete response is defined as the absence of residual invasive and in situ cancer after evaluation of the completely resected breast specimen and lymph nodes following completion of neoadjuvant systemic therapy. If a product is approved using pCR, companies must still seek full approval using event-free survival as an endpoint. About INT230-6: 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 ("SHAO") 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.