Abstract GS01-01: Biomarker Results in High-risk Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Primary Breast Cancer Following Neoadjuvant Chemotherapy ± Nivolumab: an Exploratory Analysis of CheckMate 7FL
Authors: Loi Sherene , Curigliano Giuseppe , Salgado Roberto , Díaz Roberto Iván Romero , Delaloge Suzette , García Carlos Ignacio Rojas , Kok Marleen , Saura Cristina , Harbeck Nadia , Mittendorf Elizabeth , Yardley Denise , Pusztai Lajos , Zaizar Alberto Suárez , Ungureanu Andrei , Ades Felipe , Chandra Rajalakshmi , Nathani Raheel , Pacius Misena , Spires Thomas , Wu Jenny , McArthur Heather 
Published: May 2024

Abstract
Background:
CheckMate 7FL (CM 7FL; NCT04109066) is a prospective, phase 3, randomized, multicenter, double-blind trial investigating nivolumab (NIVO) in combination with neoadjuvant chemotherapy (NACT) and adjuvant endocrine therapy (ET) in patients (pts) with high-risk, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) primary breast cancer (BC).
The primary endpoint (pathological complete response, pCR) was met, resulting in a statistically significant improvement with added NIVO to NACT; residual cancer burden (RCB) 0–1 rate was meaningfully improved. NIVO benefit was larger in pts with PD-L1+ tumors (SP142 assay, % immune cells ≥ 1%).
This analysis focuses on additional biomarkers to explore associations with NIVO treatment effect. Methods:
The study enrolled newly diagnosed pts, stages T1c–2 N1–2 or T3–4 N0–2, grade 2 (ER 1–‍10%) or 3 (ER ≥ 1%). Pts were randomized 1:1 to NACT + NIVO 360 mg Q3W/NIVO 240 mg Q2W (arm A) or NACT + placebo (PBO; arm B). Clinical efficacy data included pCR (ypT0/is ypN0) and RCB 0–1 rates in the modified ITT (mITT) population and the SP142 PD-L1+ subgroup.
Baseline PD-L1 expression from core biopsies was evaluated with the Dako 28-8 assay using the combined positive score (CPS) algorithm. Various cutoffs (CPS ≥ 1, 10, and 20) were used for this exploration. Concordance between PD-L1 SP142 and 28-8 CPS was evaluated, with assays performed on different slides from the same tumor biopsy blocks.
Results of efficacy by ER and/or progesterone receptor (PR) expression, as well as Ki67 index and stromal tumor-infiltrating lymphocytes, will be presented at the meeting. Results:
Overall, 830 pts were screened, 521 randomized, and 517 treated, with the primary efficacy population (mITT; n = 510) including all randomized pts but excluding 11 pts from Russian sites with insufficient follow-up. A total of 510 and 349 pts (68.4% of mITT population) were evaluated by PD-L1 SP142 and 28-8 CPS assays, respectively.
The prevalence of PD-L1+ by CPS was balanced in arms A and B (52% vs 50% had CPS ≥ 1; 19% vs 16% had CPS ≥ 10, and 11% vs 9% had CPS ≥ 20, respectively).
NIVO effect was larger in pts with tumors with increasing PD-L1 expression, with a ∆pCR rate (unweighted rate difference between arms A and B) of 16.6% in CPS ≥ 1 (40.4% vs 23.8% in arms A/B; 95% CI, 2.8 to 29.4), 32.4% in CPS ≥ 10 (65.7% vs 33.3% in arms A/B; 95% CI, 7.3 to 52.3), and 52.3% in CPS ≥ 20 (78.9% vs 26.7% in arms A/B; 95% CI, 18.6 to 72.4). In comparison, the ∆pCR rate was 10.7% in the mITT population (24.5% vs 13.8% in arms A/B; 95% CI, 3.9 to 17.4) and 5.7% in pts with CPS &lt; 1 (14.0% vs 8.2% in arms A/B; 95% CI, -4.0 to 15.5; refer to the Table for additional details).
Unweighted rate differences between arms A and B for RCB 0–1 (∆RCB 0–1 rate) followed a similar trend and were observed to be 17.0% in CPS ≥ 1, 34.4% in CPS ≥ 10, and 52.3% in CPS ≥ 20. In comparison, the ∆RCB 0–1 rate was 9.4% in the mITT population and 3.3% in pts with CPS &lt; 1 (refer to the Table for additional details).
Further biomarker data and cutoffs will be presented at the meeting. Conclusions:
Greater PD-L1 expression was associated with higher pCR and RCB 0–1 rates, suggesting that pts with PD-L1+, high-risk, ER+/HER2− primary BC can achieve substantial pCR rates with the addition of NIVO to NACT.
Table. Summary pCR and RCB 0–1 rates by PD-L1 SP142 and 28-8 CPS at various cutoffs. Note: CPS data with the cutoff at 5 will be presented at the meeting.
Citation Format: Sherene Loi, Giuseppe Curigliano, Roberto Salgado, Roberto Iván Romero Díaz, Suzette Delaloge, Carlos Ignacio Rojas García, Marleen Kok, Cristina Saura, Nadia Harbeck, Elizabeth Mittendorf, Denise Yardley, Lajos Pusztai, Alberto Suárez Zaizar, Andrei Ungureanu, Felipe Ades, Rajalakshmi Chandra, Raheel Nathani, Misena Pacius, Thomas Spires, Jenny Wu, Heather McArthur. Biomarker Results in High-risk Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Primary Breast Cancer Following Neoadjuvant Chemotherapy ± Nivolumab: an Exploratory Analysis of CheckMate 7FL [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS01-01.