Abstract PD7-07: Three-year event-free survival from a phase 2 study of peri-operative immune checkpoint inhibition and cryoablation in women with hormone receptor-negative, HER2-negative early stage/resectable breast cancer (ipilimumab/nivolumab cohort)

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive subtype associated with a high risk of early recurrence. Patients who do not achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have a 3-year event-free survival (EFS) of less than 60%. Preclinical and early clinical data suggest that immune checkpoint inhibition (ICI) and cryoablation (cryo) may synergize to enhance antitumor immunity. We conducted a single-arm, phase 2 study evaluating peri-operative ICI and cryo in patients with early-stage, resectable TNBC. In the initial cohort, ipilimumab (ipi) plus nivolumab (nivo) were administered. After the United States FDA approval of pembrolizumab as standard of care (SOC) for high-risk, early-stage TNBC in 2021, the study was modified to allow for SOC ICI. The pembrolizumab cohort is not yet mature for analysis. Here, we report 3-year EFS for the ipi/nivo cohort. Methods: In this prospective, single-arm, multicenter, phase 2 trial, patients aged ≥18 years with early-stage, resectable, hormone receptor-negative (ER 10%, PR 10%), HER2-negative breast cancer and ≥1.0 cm residual disease following taxane-based NAC were enrolled and treated with peri-operative ipi/nivo in combination with cryo, followed by definitive breast surgery and adjuvant nivo. Patients underwent percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and received a single dose of ipi (1 mg/kg IV) and nivo (240 mg IV) 1 to 5 days prior to cryo. Following surgery, patients received three additional doses of nivo (240 mg IV) every two weeks. Adjuvant capecitabine was recommended for all patients in accordance with local SOC. The primary endpoint was 3-year EFS defined as the time from enrollment to disease progression that precluded definitive surgery, local or distant recurrence, or death from any cause. Secondary endpoints included invasive disease-free survival (IDFS), distant disease-free survival (DDFS), overall survival (OS), and safety. Results: A total of 15 patients were enrolled and treated with peri-operative ipi/nivo and cryo. At a median follow-up of 49.5 months (data cutoff: June 1, 2025), the 3-year EFS was 66.7% (95% CI, 45.7 to 95.4). Five events were observed: four distant recurrences at 2, 10, 15, and 16 months, and one loco-regional recurrence at 25 months. The 3-year IDFS, DDFS, and OS were 66.7%, 73.3%, and 80.0%, respectively. Grade ≥3 adverse events (AEs) occurred in 6 patients (40%) with none attributed to cryo. Cryo-related AEs were limited to grade 1 breast pain in two patients (13%). Immune-related adverse events (irAEs) of any grade occurred in 5 patients (33%), with grade ≥3 irAEs reported in 2 patients (13%) including one case of adrenal insufficiency. Conclusions: Peri-operative ICI with ipi/nivo combined with cryo demonstrated encouraging long-term outcomes in patients with high-risk, early-stage TNBC who did not achieve a pCR with NAC. The 3-year EFS of 66.7% exceeds the historical benchmark of 56.8% observed in the NAC-alone arm of KEYNOTE-522. These findings suggest that cryo may enhance antitumor immunity and may allow for shorter duration of ICI. The regimen was generally well tolerated, with minimal cryo-related AEs and manageable irAEs. These results support further investigation of cryo as a strategy to augment ICI efficacy in early-stage TNBC. Citation Format: H. L. McArthur, D. B. Page, S. B. Rice, S. Reddy, P. Julien, I. Chan, B. Dogan, D. Klemow, N. Unni, J. Leal, C. Martinez, W. Mills, S. Mellinger, N. Fredrich, L. Currie, N. Moxon, M. Carter, M. Ramos, J. Curtin, S. Patil, L. Norton. Three-year event-free survival from a phase 2 study of peri-operative immune checkpoint inhibition and cryoablation in women with hormone receptor-negative, HER2-negative early stage/resectable breast cancer (ipilimumab/nivolumab cohort) 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 PD7-07.