Abstract PS5-08-27: Single arm phase II study with abemaciclib and bicalutamide in locoregionally advanced inoperable or metastatic androgen receptor-positive triple-negative breast cancer (ABBICAR)

Abstract Background: Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and has a poor prognosis, with a 5-year survival rate of only 12% in the metastatic setting. Between 20-40% of these express the androgen receptor (AR). The luminal androgen receptor (LAR) subtype of TNBC is additionally characterized by luminal gene expression. This subtype is typically less responsive to conventional chemotherapy and is mostly seen in elderly patients who more often tolerate chemotherapy poorly. Preclinical studies and early-phase clinical trials suggest that anti-androgen therapies may offer clinical benefit at a higher tolerability. Furthermore, loss-of-function alterations in the Retinoblastoma protein (RB1) are less frequent in LAR, making them more susceptible to CDK4/6 inhibition. This provides a rationale for combining abemaciclib, a CDK4/6 inhibitor, with bicalutamide, an anti-androgen—an approach not yet explored in clinical trials. Methods: ABBICAR (NCT06365788) is a multicenter single arm phase II study evaluating the efficacy and safety of bicalutamide in combination with abemaciclib in inoperable or metastatic AR-positive TNBC. Additionally, inclusion is allowed of estrogen receptor low patients (max 10 patients). A total of 53-59 patients will be enrolled, beginning with a dose-finding safety lead-in (n=6-12), followed by a Simon’s two-stage design (n=25-47). The initial dose in the safety lead-in is abemaciclib 150 mg twice daily plus bicalutamide 150 mg once daily. If after one cycle, no more than one dose-limiting toxicity (DLT) occurs in the first six patients, this dose will be used. Otherwise, safety lead-in will be repeated with abemaciclib 100 mg twice daily with the same dose of bicalutamide. The primary endpoint is disease control rate (DCR) at 16 weeks. Translational objectives include evaluation of stromal tumor-infiltrating lymphocytes, AR expression, PBMC dynamics and ctDNA in association with clinical response. The estimated duration is 48 months. Second stage of Simon’s two stage will start if a DCR of 22.6% (n>=7/31) is observed. DCR and binary endpoints will be estimated as a binomial proportion and reported with a 90% confidence interval. Results: Ethics approval has been obtained (EU CT 2022-502272-23-00; available via the EU Clinical Trials Register). Patients will be included in UZ Leuven, UZ Antwerpen, UZ Brussel, UZ Gent, Jessa Hasselt, and ZAS Antwerpen. The initial safety lead-in with abemaciclib 150 mg twice daily began in April 2024. Two DLTs (grade 3 diarrhea) were observed among the first three patients, leading to early termination of this safety lead-in. A second safety lead-in with abemaciclib 100 mg twice daily was initiated, with no DLTs nor additional safety signals observed in six additional patients. The first stage of Simon’s two-stage design began in January 2025. To date, 18 patients have been enrolled and recruitment is ongoing. Conclusion: This trial explores a novel, chemotherapy-sparing treatment strategy for AR-positive TNBC. If successful, it could offer a more tolerable alternative to conventional chemotherapy. Results from the first stage are expected in 2026. This study is funded by a grant from Kom Op Tegen Kanker. Citation Format: K. Borremans, A. Laenen, M. Maetens, P. Aftimos, H. Wildiers, G. Floris, H. Denys, C. Fontaine, A. Requilé, S. Altintas, K. Punie, C. Desmedt, P. Neven. Single arm phase II study with abemaciclib and bicalutamide in locoregionally advanced inoperable or metastatic androgen receptor-positive triple-negative breast cancer (ABBICAR) [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 PS5-08-27.