Abstract PS5-08-16: Intratumoral Injections of INT230-6 Prior to Neoadjuvant Immuno-chemotherapy in Early-Stage Triple Negative Breast Cancer: Early observations from INVINCIBLE-4-SAKK 66/22 (NCT06358573), a Phase II Randomized Controlled Trial

Abstract Background: Triple Negative Breast Cancer (TNBC) poses significant challenges due to its aggressiveness, high relapse rate and mortality. Neoadjuvant immuno-chemotherapy (NAIC) is now a common treatment for early-stage TNBC before surgery. NAIC aims to eliminate viable cancer in the tumor, lymph nodes and possible occult distant metastases, shrink tumors to improve surgical outcomes and prevent disease recurrence. The Keynote-522 study revealed a 84.5% 3-year event-free survival in patients with early-stage TNBC using NAIC and improved pathological complete response (pCR) rates from 51.2% with neoadjuvant Chemotherapy to 64.8% with NAIC. A new potential method to improve clinical outcome and induce immune activation pre-surgery is through a novel local therapy in combination with NAIC that could cause increased apoptotic cell death and create personalized tumor antigens. Arnaout et al. conducted a randomized, phase 2 neoadjuvant window of opportunity trial using intratumoral (IT) INT230-6, a drug comprising vinblastine, cisplatin and a tumor dispersion and cell penetration enhancer molecule (SHAO), evaluating clinical and biological effects in women with early-stage operable BC (NCT04781725). Results in T2 to T4 tumors showed an average of over 30% necrosis in 74% of subjects at the time of surgery, with some patients having 95% tumor necrosis following a single dose. Adding immune-activating and apoptotic induced necrosis caused by INT230-6 dosed prior to NAIC in TNBC patients has the potential to increase pCR. Methods: This is a randomized, open-label multicenter phase 2 clinical study to determine the clinical activity, safety, and tolerability of IT INT230-6 in patients with early-stage, operable TNBC in combination with NAIC (cohort A) or NAIC alone (cohort B). The INT230-6 dose is dependent on tumor size. The primary endpoint is pCR in the primary tumor (ypT0/Tis) and affected lymph nodes (ypN0). Key inclusion criteria include newly diagnosed, previously untreated, locally advanced non-metastatic TNBC stage cT1c N1-3 M0 or cT2-4c N0-3 M0. Multifocal and multicentric primary tumors are allowed. Patients must have measurable disease in the breast with at least one lesion with a diameter ≥1.5 cm visible in ultrasound and injectable. Patients are either male or female, age ≥ 18 years, ECOG performance status 2, adequate bone marrow, hepatic and renal function. STATS: The sample size calculation for both cohorts is determined based on a single-stage phase II single-arm clinical trial design (A’Hern). Null hypothesis (H0): pCR rate ≤ 0.6, Alternative hypothesis (H1): pCR rate ≥ 0.8. Type I error: 10% (one-sided), Power: 80%. The duration for accrual, patient therapy and follow-up is 12, 8 and 36 months respectively. The sample size per cohort is 27 patients. The study is recruiting in Switzerland and France in up to 16 sites. Results: By July 2025 15 of 54 patients could be enrolled, completion of accrual is expected in 2026. Preliminary safety data do not show unexpected or severe INT230-6 related adverse events. pCR results become available 6 months after the last patient starts the SOC and undergoes surgery. An exemplary case of a patient will be shown. Citation Format: U. Zürrer, A. Müller, O. Tredan, C. Micheloud, J. Musilova, R. Popescu, T. Schmid, L. Rossi, M. Schwitter, M. Vetter, M. Niemeyer, I. Witzel, A. Patsouris, S. Ladoire, J. Martin-Babau, A. Deleuze, M. Robert, L. H. Bender, M. Joerger. Intratumoral Injections of INT230-6 Prior to Neoadjuvant Immuno-chemotherapy in Early-Stage Triple Negative Breast Cancer: Early observations from INVINCIBLE-4-SAKK 66/22 (NCT06358573), a Phase II Randomized Controlled Trial abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-08-16.