A single-arm phase 2 study of peri-operative immune checkpoint inhibition 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, Philomena McAndrew, Brigid Larkin, David B. Page, Staci L. Mellinger, Nicole Fredrich, Nicole Moxon, Sangeetha M. Reddy, Meredith Carter, Sujata Patil, Basak Dogan, Margaret Elena Gatti-Mays, 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, Philomena McAndrew, Brigid Larkin, David B. Page, Staci L. Mellinger, Nicole Fredrich, Nicole Moxon, Sangeetha M. Reddy, Meredith Carter, Sujata Patil, Basak Dogan, Margaret Elena Gatti-Mays, Larry Norton Organizations University of Texas Southwestern Medical Center, Dallas, TX, Memorial Sloan Kettering Cancer Center, New York, NY, CLION-CAM Group, Salvador, Brazil, Cedars-Sinai Medical Center, West Hollywood, CA, Cedars-Sinai Medical Center, Los Angeles, CA, Cedars-Sinai Cancer, Los Angeles, CA, Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, Providence Cancer Institute, Portland, OR, Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, UTSW, Dallas, TX, Ohio State University Comprehensive Cancer Center, Columbus, OH Abstract Disclosures Research Funding Other Foundation Komen, ASCO, Bristol-Myers Squibb, BTG International Ltd Background: Local tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with immune checkpoint inhibition (ICI) augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ICI [ipilimumab (ipi) +/- nivolumab (nivo)] was safe in patients (pts) with operable, early stage breast cancer (ESBC) and generated robust intra-tumoral and systemic immune responses. In this phase 2 study, we evaluate the disease specific impact of peri-op ICI in women with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC), a subset at high risk of early relapse. Methods: Eligible women are ≥18y, with ER <10%, PR <10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. As of 2/14/21, 16/80 pts have been 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 received ipi (1mg/kg IV) with nivo (240mg IV) 1 to 5 days prior to cryo. After surgery, pts received 3 additional doses of nivo at 240mg IV Q2 weeks. To reflect the US FDA approval of curative-intent pembrolizumab (pembro) in 2021, the protocol was recently amended to allow standard-of-care pembro as an alternative ICI option. Adjuvant capecitabine or olaparib 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.

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