INT230-6 Combination Resumes Dosing in Phase 2 Presurgical TNBC Trial

Patient dosing has resumed in the randomized, open-label, multicenter phase 2 INVINCIBLE-4 trial (NCT06358573), with the first new patients receiving intratumoral INT230-6 as neoadjuvant therapy for triple-negative breast cancer (TNBC) in Switzerland, according to a news release from the company.¹

The study, also known as SAKK 66/22, is evaluating INT230-6 given before standard-of-care (SOC) neoadjuvant immuno-chemotherapy against SOC alone in patients with early-stage, operable TNBC.^1,2 Patients were randomly assigned to a single dose of INT230-6 followed by SOC—pembrolizumab (Keytruda), anthracyclines, carboplatin, cyclophosphamide, and paclitaxel—or to SOC alone, with pathological complete response (pCR) in the primary tumor and affected lymph nodes as the primary end point, tested against a null hypothesis of a pCR rate of 60% or less.

Enrollment had been paused so investigators could evaluate skin irritation reported in some patients on the combination arm. In March 2026, the company submitted a protocol amendment to Swissmedic and the Swiss Ethics Committee that lowered the drug-to-tumor volume ratio and reduced dosing to a single injection of INT230-6, changes that supported the current restart.

Before the pause, 14 patients had been treated, 7 with INT230-6 plus SOC and 7 with SOC alone; patients who received INT230-6 before SOC showed a favorable trend toward fewer grade 3 or higher adverse events (AEs), including immune-related AEs, compared with those who received SOC alone.Investigators plan to enroll an additional 47 patients across sites in Switzerland and France.

“Many [patients with] TNBC undergoing SOC treatment alone fail to achieve a [pCR] at the time of surgery, especially in larger tumor sizes,” said Markus Joerger, MD, PhD, of the Department of Medical Oncology and Hematology at Health Ostschweiz and professor of medicine at the University of Basel, who serves as study director and coordinating investigator of the trial.¹ “Early data indicate that INT230-6 has the potential to fill this unmet need for aggressive subtypes, such as TNBC, through its anti-cancer mechanisms of action that cause tumor cell necrosis and ignite an anti-cancer immune-based response,” he added, noting that reducing toxicity while inducing necrosis and immune activation ahead of surgery “would be a major advance for the treatment of breast cancer and potentially many other cancers.”

“[TNBC] is a deadly and aggressive form of breast cancer, and patients having local disease currently undergo a harsh 6-month regimen whereby a small percentage can die from the SOC before their surgery,” said Lewis H. Bender, founder, chairman, and chief executive officer of Intensity Therapeutics.¹ Bender said the company believes the amended dosing regimen “can continue to show favorable overall safety, a meaningful improvement in the percentage of patients who achieve pCR, and ultimately an improved event-free survival.”

INT230-6 combines the cytotoxic agents cisplatin and vinblastine sulfate with a diffusion and cell-penetration enhancer molecule that non-covalently conjugates to both payload drugs, allowing the agents to disperse throughout the tumor and penetrate cancer cells while remaining largely localized to the injection site. Beyond direct tumor cell killing, the intratumoral injection is designed to release tumor-specific neoantigens that engage the immune system and produce systemic anti-tumor effects without the immunosuppression associated with systemic chemotherapy.

Following the phase 3 KEYNOTE-522 trial (NCT03036488), standard neoadjuvant treatment for TNBC has included pembrolizumab combined with anthracyclines, cyclophosphamide, paclitaxel, and carboplatin, a regimen associated with a pCR rate of 63% and grade 3 or higher treatment-related AEs in 80% of patients, including treatment-related deaths in 0.5% of patients.³

INVINCIBLE-4 is currently enrolling across 9 locations.² Eligible patients must be at least 18 years old and have measurable disease staged as cT1c (1.5-2 cm) N1-3 M0 or cT2-4c N0-3 M0 per American Joint Committee on Cancer 8th edition criteria, with at least 1 lesion that is 1.5 cm or larger in diameter that is evaluable by RECIST v1.1, visible on ultrasound, and injectable; multifocal or multicentric disease is permitted provided TNBC is confirmed in each focus. Adequate bone marrow function is also required for eligibility.

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. Intensity Therapeutics, Inc. July 15, 2026. Accessed July 16, 2026. https://tinyurl.com/43h3cz9n
2. Intratumoral INT230-6 followed by neoadjuvant immuno-chemotherapy in patients with early TNBC. INVINCIBLE-4-SAKK. Updated April 2, 2026. Accessed July 16, 2026. https://tinyurl.com/yr7xmj93
3. Schmid P, Cortes J, Dent R, et al. Overall survival with pembrolizumab in early-stage triple-negative breast cancer. N Engl J Med. 2024;391(21):1981-1991. doi:10.1056/NEJMoa2409932