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.

Baricitinib in patients with rheumatoid arthritis with inadequate response to methotrexate: results from a phase 3 study.

OBJECTIVES: This study evaluated the efficacy and safety of baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX) therapy. METHODS: In this phase 3, double-blind, 52-week, placebo-controlled study, 290 patients with moderately to severely active RA and inadequate response to MTX were randomly assigned 1:1 to placebo or baricitinib 4-mg once daily, stratified by country (China, Brazil, Argentina) and presence of joint erosions. Primary endpoint measures included American College of Rheumatology 20% response (ACR20) at week 12. Secondary endpoints included changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) and Disease Activity Score for 28-joint counts (DAS28)-high-sensitivity C-reactive protein (hsCRP), Simplified Disease Activity Index (SDAI) score ≤3.3, mean duration of morning joint stiffness, severity of morning joint stiffness numeric rating scale (NRS 0-10), worst tiredness NRS, and worst joint pain NRS at week 12. RESULTS: Most patients (approximately 80%) were from China. More patients achieved ACR20 response at week 12 with baricitinib than with placebo (58.6% vs. 28.3%; p<0.001). Statistically significant improvements were also seen in HAQ-DI, DAS28-hsCRP, morning joint stiffness, worst tiredness, and worst joint pain in the baricitinib group compared to placebo at week 12. Through week 24, rates of treatment-emergent adverse events, including infections, were higher for baricitinib compared to placebo, while serious adverse event rates were similar between baricitinib and placebo. CONCLUSIONS: In patients with RA who had an inadequate response to MTX, baricitinib was associated with significant clinical improvements as compared with placebo.