Abstract OT-33-01: Combination ipatasertib and atezolizumab to prevent recurrence in triple negative breast cancer(TNBC): A phase II single arm trial

Abstract

Background: TNBC patients with residual disease after neoadjuvant chemotherapy (NAC) have high recurrence rates. Targetable mechanisms likely responsible for NAC resistance must therefore be identified to identify new therapeutic options. Alterations in the PI3K/mTOR pathway as well as expression of the immune checkpoint PD-L1 have emerged as potential targets, with significant frequency of alteration in TNBC. Importantly, the AKT inhibitor ipatasertib (ipat) and the anti-PD-L1 antibody atezolizumab (atezo) have demonstrated activity against TNBC. Recent data suggests that the presence of circulating tumor cell-free DNA (cfDNA) following NAC correlates with residual disease and a higher recurrence risk. We have hypothesized that combination therapy with ipat and atezo will target micrometastatic disease, as determined by the presence of cfDNA after NAC, in TNBC patients. Trial design:Open label single-arm phase II study to evaluate combination therapy with ipat and atezo, in TNBC patients with detectable cfDNA after completion of NAC, definitive surgery, and adjuvant radiation and/or chemotherapy. Eligible patients will receive: atezo [840mg IV days 1 and 15 and ipat [400 mg orally daily on days 1-21, followed by one week off] in a 28-day cycle for 6 cycles; cfDNA will be evaluated after 3 and 6 cycles. Biomarkers including PD-L1 expression on tumor cells or infiltrating immune cells in the primary tumor or PD-L1 expression on circulating tumor cells will be assessed. Eligibility criteria:Patients ≥ 18 yrs of age with pathologically confirmed residual invasive TNBC (ER and PR negative defined as Citation Format: Elizabeth Mittendorf, Sara Tolaney, Paul Wileyto, Michelle DeMeo, Hope Rugo, Rita Nanda, Ingrid Mayer, Ben Park, Heather MacArthur, Angela DeMichelle. Combination ipatasertib and atezolizumab to prevent recurrence in triple negative breast cancer(TNBC): A phase II single arm trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-33-01.