ToPCourT protocol: a phase II trial of trilaciclib, pembrolizumab, gemcitabine, and carboplatin in locally advanced/unresectable or metastatic triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a clinically aggressive and difficult to treat malignancy. It has a poorer prognosis when compared to the hormone receptor (HR)-positive and human epidermal growth factor receptor type 2 (HER2)-positive subtypes. Due to the lack of targetable receptors, cytotoxic chemotherapy is often the backbone of therapy. Although effective, its use eventually becomes limited due to toxicity and resistance. Trilaciclib is an intravenous cyclin-dependent kinase (CDK) 4/6 inhibitor. Preclinical data showed that transient CDK4/6 inhibition with trilaciclib enhances and lengthens the duration of antitumor responses induced by a combination of chemotherapy and immune checkpoint inhibition. Herein, we describe the design and rationale for ToPCourT, an open label, single-arm, phase II trial. This study will evaluate the efficacy of trilaciclib in combination with pembrolizumab, gemcitabine, and carboplatin in patients with locally advanced unresectable or metastatic TNBC who have received ≤3 lines of therapy in the metastatic setting. The primary endpoint is overall response. Key secondary endpoints include progression-free survival, duration of response, and overall survival.<b>Clinical trial registration:</b> www.clinicaltrials.gov identifier is NCT06027268.