Abstract OT2-04-03: Nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL
Authors: Loi Sherene , McArthur Heather , Harbeck Nadia , Pusztai Lajos , Delaloge Suzette , Letrent Kristen , Chen Tian , Li Bin , Tatsuoka Kay , Zardavas Dimitrios , Curigliano Giuseppe 
Published: March 2020

Abstract
Background: Estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) primary breast cancer (BC) includes a group of heterogeneous tumors, spanning from biologically indolent, ER signaling-driven to aggressive, endocrine-resistant tumors. Patients (pts) diagnosed with ER+, HER2− BC of high grade and/or low ER expression are at increased risk of relapse, despite current standard of care (SoC): chemotherapy and endocrine treatment (ET) in the neo- and adjuvant settings, respectively. New treatment options to increase cure rates are needed. Increased understanding of ER+, HER2− BC immune biology show an enrichment of cases with tumor cell recognition by the immune system and immune suppression mediated via programmed-death-1 (PD-1) signaling in pts with high-risk disease. Such features, linked with poorer prognosis and potential ET resistance, may be addressed through PD-1 inhibition combined with current SoC for pts with high-risk ER+, HER2− BC. Promising data assessing PD-1 inhibition coupled with neoadjuvant chemotherapy for pts with high-risk ER+, HER2− BC noted improved pathologic complete response (pCR) which is identified as a valid surrogate endpoint for long-term clinical outcomes. Trial Design: CheckMate 7FL is a randomized, double-blind, placebo-controlled, multicenter, global phase 3 study evaluating nivolumab (NIVO) vs placebo (PBO) in combination with neoadjuvant chemotherapy and adjuvant ET in pts with high-risk, ER+, HER2− primary BC. Eligible pts are male or female, aged ≥18 years with newly diagnosed grade 2 with ER expression of 1-9%, or grade 3, T1c-2, cN1-2 (tumor size &gt;2 cm) centrally confirmed ER+, HER2− BC. Pts eligible for neoadjuvant chemotherapy and surgery, with adequate organ function, ECOG PS of 0 or 1, and tissue available for biomarker assessments will be enrolled. Pts with history of ipsilateral invasive BC regardless of treatment, ipsilateral ductal carcinoma in situ treated with radiotherapy, contralateral invasive BC at any time, grade ≥1 peripheral neuropathy, or those with prior treatment for the currently diagnosed BC are excluded. Approximately 1200 pts will be randomized 1:1 to NIVO or PBO, stratified by programmed death ligand 1 (PD-L1) expression (+ or −), tumor grade (2 or 3), axillary nodal status (+ or −), and anthracycline + cyclophosphamide schedule (Q3W or Q2W). Node negative pts will be capped at 20% of the intent-to-treat population. In the neoadjuvant phase, pts will receive NIVO 360 mg Q3W or PBO plus paclitaxel 80 mg/m2 QW for four 3-week cycles, followed by NIVO 360 mg Q3W (or 240 mg Q2W) or matching PBO in combination with either doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 Q3W (or Q2W, respectively, dose-dense schedule option) for 4 cycles. Pts will undergo surgery after completion of the neoadjuvant phase. Following surgery, pts will enter the adjuvant phase and receive NIVO 480 mg Q4W or PBO for 7 cycles plus investigator’s choice of ET per local SoC. Primary endpoints are pCR, defined as no histologic evidence of invasive tumor cells in breast and axillary lymph nodes as well as non-axillary sentinel node (ypT0/is, ypN0) as determined by local pathologist, and event-free survival. Secondary endpoints include overall survival, disease-free survival, distant-metastasis-free survival, safety, pCR (ypT0 ypN0 and ypT0/is) rates, overall response rate, residual cancer burden, and quality of life. pCR rates will be compared using a 2-sided stratified Cochran-Mantel-Haenszel test with alpha = 0.01. Event-free survival will be compared using a stratified 2-sided log-rank test with adjusted alpha at each interim analysis and at final analysis. Recruitment worldwide is expected to begin in November 2019. For further information, please contact Kristen.Letrent@bms.com.
Citation Format: Sherene Loi, Heather McArthur, Nadia Harbeck, Lajos Pusztai, Suzette Delaloge, Kristen Letrent, Tian Chen, Bin Li, Kay Tatsuoka, Dimitrios Zardavas, Giuseppe Curigliano. Nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL [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 OT2-04-03.