A single-arm, phase 2 study of perioperative ipilimumab, nivolumab, and cryoablation in women with hormone receptor-negative, HER2-negative, early-stage/resectable breast cancer.

Heather L. McArthur University of Texas Southwestern Medical Center, Dallas, TX info_outline Heather L. McArthur, Elizabeth Anne Comen, Yolanda Bryce, Stephen Barnett Solomon, Jorge Henrique S. Leal, Christina DiLauro Abaya, Cristal Martinez, Reva K Basho, Dorothy J. Park, Philomena McAndrew, Brigid Larkin, William Mills, David B. Page, Staci L. Mellinger, Nicole Fredrich, Nicole Moxon, Sangeetha M. Reddy, Meredith Carter, Sujata Patil, Larry Norton

Authors Heather L. McArthur University of Texas Southwestern Medical Center, Dallas, TX info_outline Heather L. McArthur, Elizabeth Anne Comen, Yolanda Bryce, Stephen Barnett Solomon, Jorge Henrique S. Leal, Christina DiLauro Abaya, Cristal Martinez, Reva K Basho, Dorothy J. Park, Philomena McAndrew, Brigid Larkin, William Mills, David B. Page, Staci L. Mellinger, Nicole Fredrich, Nicole Moxon, Sangeetha M. Reddy, Meredith Carter, Sujata Patil, Larry Norton Organizations University of Texas Southwestern Medical Center, Dallas, TX, Memorial Sloan Kettering Cancer Center, New York, NY, CLION-CAM Group, Salvador, Brazil, UT Southwestern, Dallas, TX, Cedars-Sinai Medical Center, West Hollywood, CA, Cedars-Sinai Medical Center, Houston, TX, Twr Hem Onc Med Grp, Beverly Hills, CA, Twr Hem Onc Medcl Grp, Beverly Hills, CA, Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, Cedars-Sinai Medical Center, Los Angeles, CA, Earle A. Chiles Research Institute at the Robert W. Franz Cancer Center, Portland, OR, Providence Cancer Center, Portland, OR, Providence Portland Medical Center, Portland, OR, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Conquer Cancer Foundation of the American Society of Clinical Oncology, Other Foundation, BTG 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 phase 2 study, we evaluate the disease specific impact of peri-op ipi/nivo/cryo 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 80 pts will be enrolled and treated with ipi/nivo/cryo followed by breast surgery and adjuvant nivo. Pts 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. Clinical trial information: NCT03546686.