Abstract OT1-01-04: A randomized phase 2 study of peri-operative ipilimumab, nivolumab and cryoablation versus standard care in women with residual, early stage/resectable, triple negative breast cancer after standard-of-care neoadjuvant chemotherapy

Abstract

Abstract Background: Local tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with checkpoint inhibition augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ipilimumab (ipi) +/- nivolumab (nivo) was not only safe in patients (pts) with operable, early stage breast cancer (ESBC) but also generated robust intra-tumoral and systemic immune responses. In this randomized phase 2 study, we evaluate the disease specific impact of peri-op ipi/nivo/cryo versus standard care in women with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC), a subset at high risk of early relapse. Methods: Eligible pts are ≥18y, with ER <10%, PR <10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. Approximately 160 pts will be randomized to one of two arms: breast surgery (control arm) or ipi/nivo/cryo followed by breast surgery and adjuvant nivo (intervention arm). Pts in the intervention arm will undergo percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and will receive ipi (1mg/kg IV) with nivo (240mg IV) 1 to 5 days prior to cryo. After surgery, pts will receive 3 additional doses of nivo at 240mg IV Q2 weeks. Adjuvant capecitabine is recommended for all patients per local standard-of-care. Patients will be stratified by NAC platinum administration, NAC anthracycline administration, and clinical nodal status (positive versus negative). The primary endpoint is 3-year Event Free Survival (EFS). Secondary endpoints include Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore predictors of efficacy and toxicity. Citation Format: Heather McArthur, Elizabeth Comen, Yolanda Bryce, Stephen B Solomon, Jorge Leal, Micaela Rodine, Christina DiLauro Abaya, Sujita Patil, David Page, Larry Norton. A randomized phase 2 study of peri-operative ipilimumab, nivolumab and cryoablation versus standard care in women with residual, early stage/resectable, triple negative breast cancer after standard-of-care neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-01-04.