Diego Kaen

Abstract Background: Atirmociclib (PF-07220060) is a novel potent CDK4-selective inhibitor (CDK4i) with significant sparing of CDK6. In an ongoing phase 1/2a trial, atirmociclib plus endocrine therapy showed favorable tolerability and clinical activity in patients with metastatic breast cancer (mBC) who progressed on prior CDK4/6i (Yap, et al. Ann Oncol. 2024;[suppl_4]:1-47; Abstract 184MO). Here, we present the efficacy and safety results from an expansion cohort in the phase 1/2a study of atirmociclib in combination with letrozole in treatment-naïve patients with HR+/HER2– mBC (cohort 2B). Methods: Women with HR+/HER2− mBC who had not received any prior systemic anti-cancer therapies for their advanced disease were enrolled in expansion cohort 2B of the phase 1/2a study. Patients received 300 mg BID atirmociclib + letrozole. Primary objective was to assess the safety and tolerability of atirmociclib + letrozole; a secondary objective was to evaluate the anti-tumor activity by objective response (OR = complete response [CR] + partial response [PR]) and clinical benefit rate (CBR = OR or ≥ 24 weeks stable disease) per RECIST v1.1. Results: At data cutoff (March 4, 2024), 34 patients had received atirmociclib + letrozole. Median age was 59.0 years (range 32–84); 67.6% were White, 23.5% were Asian; most had ECOG PS of 1 (55.9%). In this cohort of patients who had not received any prior systemic anti-cancer therapies in the advanced/metastatic setting, 55.9% underwent anticancer surgery and 47.1% had prior adjuvant/neoadjuvant therapy. Treatment-related adverse events (TRAEs) occurred in 28 (82.4%) patients; none were Grade (G) 4-5. Most common TRAEs were neutropenia (61.8%; 23.5% G3), leukopenia (38.2%; no G3), anemia (20.6%; no G3), and lymphopenia (20.6%; 2.9% G3). Due to a TRAE, 1 patient (2.9%) discontinued atirmociclib (G3; increased aspartate aminotransferase) and 3 (8.8%) had dose reductions (G1 and G2; neutropenia). Median relative dose intensity (RDI) of atirmociclib was 99.1% (range 36.0–100); 91.2% had RDI > 80%. Of the 32 patients who had measurable disease at baseline, 50% (16/32 patients) showed a confirmed OR, all of which were PRs. The CBR for these patients was 96.9% (31/32 patients). Among the entire cohort of 34 patients, median progression-free survival has not been reached. Median duration of follow-up was 11.1 months (95% CI 10.9–13.6). Updated efficacy data with longer follow-up will be presented at the meeting. Conclusions: Combination of atirmociclib + letrozole showed favorable safety/tolerability and promising early activity as first-line treatment in patients with HR+/HER2– mBC. Citation Format: Antonio Giordana, Manuel Magallanes, Binghe Xu, Diego Kaen, Ernesto Korbenfeld, Min Yan, Omar Zayas Villanueva, Carlos Alberto Hernandez, Peter Schmid, Michal Mego, Santiago Bella, Xinhong WU, Feng Liu, Cynthia Basu, Jennifer Park, Heather Neumann, Maria Delioukina, Timothy A. Yap. The next-generation CDK4-selective inhibitor atirmociclib (PF-07220060) in combination with letrozole as first-line treatment in patients with HR+/HER2+ metastatic breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-07-28.