Abstract PO4-19-05: OptimICE-pCR: De-escalation of therapy in early-stage TNBC patients who achieve pCR after neoadjuvant chemotherapy with checkpoint inhibitor therapy (Alliance A012103)

Abstract Background: For patients with stage II-III triple-negative breast cancer (TNBC), standard of care systemic therapy consists of neoadjuvant pembrolizumab with chemotherapy, followed by 27 weeks of adjuvant pembrolizumab based on the results of the phase III KEYNOTE-522 trial. This trial demonstrated that pathologic complete response (pCR) rates and event-free survival (EFS) were significantly better among patients who received neoadjuvant followed by adjuvant pembrolizumab in addition to chemotherapy compared to chemotherapy alone. An exploratory analysis from this study demonstrated better EFS among patients who experienced a pathologic complete response (pCR) to neoadjuvant therapy compared to those with residual disease. Additionally, other studies, including GeparNuevo, which did not include adjuvant checkpoint inhibition, demonstrated EFS benefit from the addition of preoperative checkpoint inhibitor therapy to chemotherapy. It is therefore unclear if adjuvant pembrolizumab improves outcomes for patients with early-stage TNBC who achieve a pCR after neoadjuvant pembrolizumab plus chemotherapy. OptimICE-pCR trial utilizes response to preoperative therapy to tailor adjuvant therapy, and the goal is to determine whether patients who achieve pCR to pembrolizumab plus chemotherapy can achieve a similar recurrence-free survival (RFS) with observation compared to adjuvant pembrolizumab monotherapy Methods: OptimICE-pCR is an open-label, multicenter, randomized phase III trial that is enrolling patients with stage T1cN1-2 or T2-4N0-2 TNBC. To be eligible, patients must have experienced a pCR after the completion of neoadjuvant therapy containing a minimum of six cycles of chemotherapy in combination with pembrolizumab. Participants are randomized 1:1 to receive either 27 weeks of adjuvant pembrolizumab or to observation. Participants on the pembrolizumab arm receive pembrolizumab 200 mg IV on day 1 of each 21-day cycle for 9 cycles, or 400 mg IV on day 1 of each 42-day cycle for 4 cycles, followed by one dose of 200 mg IV every 21 days. The primary objective is to evaluate whether observation results in non-inferior RFS compared to adjuvant pembrolizumab. Non-inferiority is defined as an estimated 3-year RFS of 91% or higher in the observation arm compared to 94% in the pembrolizumab arm. The total sample size will be 1,295 patients, which will provide 80% power at one-sided significance level of 0.05 to detect this difference, which corresponds to a non-inferiority hazard ratio of 1.52. Key secondary endpoints include overall survival, locoregional recurrence, quality of life, financial toxicity, work productivity impairment, cost-effectiveness, and safety and tolerability. Key correlative objectives include detection of ctDNA at baseline and association with RFS and association of key biomarkers (TILs, PDL1, immune gene expression) from the primary tumor with RFS. The trial is currently open and enrolling patients. Support: U10CA180821, U10CA180882; U24 CA196171; U10CA180820 (ECOG-ACRIN); U10CA180863 (CCTG); https://acknowledgments.alliancefound.org. ClinicalTrials.gov Identifier: NCT05812807 Citation Format: Sara Tolaney, Karla Ballman, Charles M Perou, David Cescon, Margaret Gatti-Mays, Victoria Blinder, Shoshana Rosenberg, Elizabeth Mittendorf, Anna Weiss, Hope Rugo, Alice Ho, Dana Casey, Baljit Singh, Fabrice Smieliauskas, Yara Abdou, Vijay Damarla, Jane Meisel, Lisa Carey, Ann Partridge. OptimICE-pCR: De-escalation of therapy in early-stage TNBC patients who achieve pCR after neoadjuvant chemotherapy with checkpoint inhibitor therapy (Alliance A012103) 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 PO4-19-05.