Phase 2 Presurgical Breast Cancer Trial Resumes After Dosing Pause for Skin Toxicity

Enrollment has resumed in a randomized phase 2 trial (NCT06358573) testing an investigational intratumoral therapy, INT230-6, before standard neoadjuvant treatment in early-stage triple-negative breast cancer (TNBC), following a temporary pause to address skin irritation observed in earlier patients.¹

The first patients under the amended protocol have been dosed in Switzerland. INT230-6 is an investigational combination of cisplatin, vinblastine sulfate, and a proprietary diffusion-enhancing molecule designed for direct injection into tumors.

Trial Background

The trial, known as INVINCIBLE-4, is a randomized, open-label, multicenter study evaluating INT230-6 given before standard-of-care neoadjuvant immunochemotherapy compared with standard care alone in patients with operable TNBC. The primary end point is pathological complete response (pCR) in the primary tumor and axillary lymph nodes, assessed against a null hypothesis of a pCR rate of 60% or less.²

Fourteen patients were treated before accrual was paused—7 who received INT230-6 followed by standard therapy and 7 who received standard therapy alone. Patients who received INT230-6 before standard treatment showed a trend toward fewer grade 3 or higher adverse events, including immune-related adverse events, compared with those who received standard therapy alone. In March 2026, Intensity Therapeutics submitted a protocol amendment to Swissmedic and the Swiss Ethics Committee to resume enrollment using a lower drug-to-tumor volume ratio administered as a single injection. The study is expected to enroll 47 additional patients across sites in Switzerland and France.¹

Under the amended protocol, patients are randomized to receive a single dose of INT230-6 followed by standard neoadjuvant therapy—pembrolizumab (Keytruda) plus anthracycline, carboplatin, cyclophosphamide, and paclitaxel—or to standard therapy alone.

"Many [patients with TNBC] undergoing [standard-of-care] treatment alone fail to achieve a [pCR] at the time of surgery, especially in larger tumor sizes. Early data indicates that INT230-6 has the potential to fill this unmet need for aggressive subtypes, such as TNBC, through its anticancer mechanisms of action that cause tumor cell necrosis and ignite an anti-cancer immune-based response," said Markus Joerger, MD, PhD from the Department of Medical Oncology and Hematology at Health Ostschweiz, professor of medicine at the University of Basel, co-chair of the SCI's Project Group for Developmental Therapeutics, and coordinating investigator of the trial, in a news release. "The ability for INT230-6 to induce necrosis and activate immune effects before a patient's surgery with reduction in toxicity would be a major advance for the treatment of breast cancer and potentially many other cancers."

TNBC accounts for an estimated 11% to 17% of breast cancers and lacks expression of estrogen receptor, progesterone receptor, and HER2, limiting the availability of targeted therapies. Since the KEYNOTE-522 trial (NCT03036488), standard neoadjuvant treatment for TNBC has combined systemic chemotherapy with the anti–PD-1 antibody pembrolizumab.³ Under that regimen, pCR rates are approximately 63%, with lower rates in larger (T2–T4) tumors, and roughly 80% of patients experience grade 3 or higher treatment-related adverse events, including treatment-related death in 0.5% of cases.

Development Program

Intensity Therapeutics has completed 3 earlier studies of INT230-6 involving more than 200 patients: a phase 1/2 dose-escalation study in metastatic cancers, including sarcomas (NCT03058289), and a randomized phase 2 study in locally advanced breast cancer, INVINCIBLE-2 (NCT04781725).¹ A phase 3 trial in soft tissue sarcoma, INVINCIBLE-3 (NCT06263231), is evaluating INT230-6 as second- or third-line monotherapy against standard care, with overall survival as the primary endpoint. INVINCIBLE-4 is being conducted in collaboration with the Swiss Cancer Institute as part of a broader phase 2/3 development program.

REFERENCES

1. Intensity Therapeutics, Inc. Restarts Patient Treatment in the Randomized, Presurgical Triple Negative Breast Cancer Phase 2 Clinical Trial (INVINCIBLE-4 Study). News release. July 15, 2026. Accessed July 16, 2026. https://tinyurl.com/zkzxr6n8

2. Intratumoral INT230-6 Followed by Neoadjuvant Immuno-chemotherapy in Patients With Early TNBC. INVINCIBLE-4-SAKK. ClinicalTrials.gov. Updated April 2, 2026. Accessed July 15, 2026. https://clinicaltrials.gov/study/NCT06358573

3. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549. PMID: 32101663.