Abstract PD7-10: Neo-n (neon): three-year event-free survival and ultrasensitive ctdna dynamics in early triple-negative breast cancer (tnbc) treated with neoadjuvant carboplatin/paclitaxel and nivolumab

Abstract Background The Neo-N trial previously showed a pathological complete response (pCR) rate of 53% with 12 weeks of carboplatin/paclitaxel plus nivolumab. We report 3-year EFS and associations of an ultrasensitive tumor-informed structural-variant (SV)–based circulating tumor DNA (ctDNA) assay with EFS. Methods Neo-N is an investigator-initiated, non-comparative, open-label, randomized phase 2 trial across 14 sites. Adults with operable stage I–II TNBC received carboplatin AUC5 q3w + weekly paclitaxel for 12 weeks with nivolumab per assigned schedule- A: lead in monotherapy or B: concurrent Nivolumab, followed by surgery and adjuvant therapy per investigator. A cohort underwent tumor-informed ctDNA SV assay derived from whole genome sequencing and plasma was collected at: T0 (baseline) and T1 (5+/-1 weeks) and T2 28 days post-surgery. Primary objectives of this report are 3-year EFS and association of ctDNA status and dynamics, as well as tumor infiltrating lymphocyte (TIL) changes with EFS. Results As of the planned data cutoff median follow-up is 36 months (range 20-43mo). Among all randomized participants (n=108), the 36mo EFS rate is 92.4% (90% CI 83.5-96.6%) for cohort A and for B 83.1% (90% CI: 72.4% to 89.9%). 59% (64/108) had ≥1 ctDNA assay timepoint. Baseline T0 ctDNA was detectable in 91% with median ctDNA tumor fraction = 0.3526% (P25 = 0.0481, P75 = 1.856; range 0–28.61). At T1 and T2, ctDNA was detectable in 18% (11/62) and 4% (2/56), respectively. There was comparable early ctDNA clearance at T1 across the two cohorts (A 76% vs B 77%) despite less chemotherapy exposure in Cohort A. T1 ctDNA + had no pCRs and 36mo EFS of 45.5% (90% CI: 20.8% to 67.3%); T1 ctDNA- had a pCR rate of 58.8% and EFS of 91.5% (90% CI: 81.5% to 96.2%). Across ctDNA dynamics: T0-T1 74% (46/62) went from Pos to Neg i.e. cleared ctDNA and had a pCR rate 63.0% (90% CI: 49.9% to 74.9%), EFS 90.6% (90% CI: 79.6% to 95.8%) vs Pos-Pos had 0 pCRs (n=11), EFS 45.5% (90% CI: 20.8% to 67.3%)and Neg-neg (n=5) had a 100% EFS. No new safety signals were observed; immune-related adverse events were consistent with prior reporting. Full efficacy (EFS/Overall survival), TIL and ctDNA data will be presented. Conclusions A short-course, non-anthracycline carboplatin/paclitaxel plus nivolumab achieves durable 3-year disease control in early TNBC. An on treatment tumor-informed SV-ctDNA measurement is associated with EFS, complementing surgical endpoints. These findings support ultrasensitive ctDNA for risk-stratification tool and provide a rationale for early on treatment ctDNA-guided escalation/de-escalation strategies to refine neoadjuvant chemo-immunotherapy for early TNBC patients. Citation Format: S. Loi, S. M. Niman, N. Zdenkowski, N. Segui, P. A. Francis, S. Baron Hay, W. Fox, K. Punie, A. M. Menzies, R. Angus, S. Zardawi, B. Mitchell, C. Mavin, S. Dawson, K. Howarth, M. J. J. Kuper-Hommel, M. M. Regan. Neo-n (neon): three-year event-free survival and ultrasensitive ctdna dynamics in early triple-negative breast cancer (tnbc) treated with neoadjuvant carboplatin/paclitaxel and nivolumab abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD7-10.