A Randomized Phase I Study of Abemaciclib in Chinese Patients with Advanced and/or Metastatic Cancers

Background Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, is approved in combination with endocrine therapy or as monotherapy for hormone receptor-positive and human epidermal growth factor receptor-2-negative (HR+/HER2−) advanced breast cancer outside of China. Objective To evaluate the safety, tolerability, and pharmacokinetic (PK) profile of abemaciclib in Chinese patients with advanced and/or metastatic cancers. Patients and methods A multicenter, open-label, phase I trial of abemaciclib in Chinese patients with advanced and/or metastatic cancers was conducted. Patients were randomized (1:1) to oral abemaciclib 150 or 200 mg every 12 h on a 28-day cycle. Safety analyses (primary outcome) included all patients receiving at least one dose of abemaciclib. PK and antitumor activity were also assessed. Results Of the 26 patients randomized, 25 received abemaciclib 150 mg ( n = 12) or 200 mg ( n = 13). All 25 patients reported ≥ 1 treatment-emergent adverse event (TEAE). The majority of TEAEs were Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or 2 in severity. The most frequent TEAEs of Grade ≥ 3 were neutropenia (32%) and thrombocytopenia (24%). Four patients (16%) discontinued treatment due to AEs. Abemaciclib exhibited slow absorption and clearance at single dose, with maximum concentrations achieved after around 6 h and an elimination half-life of approximately 24 h. No complete response was observed, two patients (8%) achieved partial response, with one confirmed responder, and the disease control rate was 68% ( n = 17). Conclusions Abemaciclib was well tolerated and the safety and PK profiles in Chinese patients were comparable to those previously reported in non-Chinese populations. Preliminary antitumor activity was observed. ClinicalTrials.gov identifier NCT02919696.