Abstract CT108: A phase 1b study of abemaciclib in combination with pembrolizumab for patients (pts) with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC) (NCT02779751): Preliminary results
Authors: Rugo Hope S. , Beck J. Thad , Jerusalem Guy , Wildiers Hans , Kabos Peter , Chisamore Michael , McNaughton Rhian , Chen Yanyun , Hossain Anwar , Tolaney Sara M. 
Published: September 2020

Abstract
Background: Abemaciclib is an orally administered, selective small molecule cyclin-dependent kinase (CDK) 4 and 6 inhibitor, approved to treat HR+, HER2- mBC pts on a continuous twice daily dosing schedule as monotherapy or in combination with endocrine therapy (ET), an aromatase inhibitor as initial endocrine based therapy, or in combination with fulvestrant. In preclinical models, abemaciclib monotherapy induced intra-tumoral immune inflammation and had a synergistically enhanced anti-tumor efficacy when administered in combination with programmed cell death protein 1 blockade. Here we report the safety and preliminary anti-tumor activity of abemaciclib plus pembrolizumab plus anastrozole in HR+, HER2- locally advanced or mBC pts. Methods: This multicenter, nonrandomized, open-label, multi-cohort phase 1b study of abemaciclib plus pembrolizumab plus anastrozole enrolled a cohort of post-menopausal HR+, HER2- pts with locally advanced or mBC. No prior CDK4/6 inhibitor, chemotherapy, or ET for locoregional advanced or mBC were allowed. Patients received 150-mg abemaciclib orally every 12 hours plus pembrolizumab 200 mg intravenously on day 1 every 21 days plus anastrozole 1 mg orally every 24 hours. The primary objective was to characterize the safety of abemaciclib plus pembrolizumab plus anastrozole. Key secondary objectives included objective response rate (ORR), progression-free survival, and overall survival. Results: Out of 26 pts enrolled, 13 (50%) had received prior systemic anti-cancer therapy, including 12 (46%) who had received ET in the adjuvant setting. The majority of pts had visceral disease (65%); 54% had 3 or more metastatic sites. The nature of adverse events (AEs) observed for the triplet therapy was overall consistent with the known side effects of abemaciclib, pembrolizumab and anastrozole. Grade 3/4 AEs in &gt; 2 pts included increased alanine aminotransferase and neutropenia (8 pts each, 31%) and increased aspartate aminotransferase (6 pts, 23%). In general, Grade 3/4 AEs were reversible following drug holds and corticosteroid treatment. There were 2 fatal events as a result of pneumonitis. Fifteen pts (58%) discontinued treatment including 9 pts (35%) due to an AE (7 transaminase elevations). Preliminary response assessment showed 5 pts had a confirmed partial response (19% ORR), and disease control rate (CR+PR+SD) was 77%. Clinical benefit rate (CR+PR+SD persisting for ≥6 months) was 27%. Conclusions: Abemaciclib plus pembrolizumab plus anastrozole demonstrated a numerically higher rate of transaminase elevations and pneumonitis than reported for the individual treatments and 2 experienced a fatal AE. At this time, evaluation of anti-cancer activity is premature.
Citation Format: Hope S. Rugo, J. Thad Beck, Guy Jerusalem, Hans Wildiers, Peter Kabos, Michael Chisamore, Rhian McNaughton, Yanyun Chen, Anwar Hossain, Sara M. Tolaney. A phase 1b study of abemaciclib in combination with pembrolizumab for patients (pts) with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC) (NCT02779751): Preliminary results [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT108.