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16.06.2016 | Original Article

Phase 1 study of abemaciclib, an inhibitor of CDK 4 and 6, as a single agent for Japanese patients with advanced cancer

verfasst von: Yutaka Fujiwara, Kenji Tamura, Shunsuke Kondo, Yuko Tanabe, Satoru Iwasa, Akihiko Shimomura, Shigehisa Kitano, Ken Ogasawara, P. Kellie Turner, Joji Mori, Hiroya Asou, Edward Michael Chan, Noboru Yamamoto

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2016

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Abstract

Purpose

To confirm the safety and tolerability, evaluate the pharmacokinetics (PK), and investigate the antitumor activity of abemaciclib in Japanese patients with advanced cancer.

Methods

We conducted a non-randomized, single-arm, open-label, dose-escalation phase 1 study of abemaciclib administered orally every 12 h (Q12H) on a 28-day cycle at doses of 100 mg (Cohort 1, n = 3), 150 mg (Cohort 2, n = 3), or 200 mg [Cohort 3, n = 6, maximum tolerated dose (MTD)]. Dose escalation was based on the frequency of dose-limiting toxicity (DLT). MTD, as established in the previous phase 1 study in non-Japanese patients, was the highest dose level at which <33 % of patients experienced DLT.

Results

Eleven of the 12 patients who received treatment with abemaciclib discontinued: 10 patients due to progressive disease, and 1 due to a DLT (Cohort 3, grade 2 nausea). Diarrhea, the most common treatment-emergent adverse event (AE), was managed supportively and did not require study treatment discontinuation. There were no drug-related serious AEs and no patients with corrected QT (QTc) > 480 ms or QTc change of >60 ms from baseline. The abemaciclib PK profile was characterized by slow absorption and high PK variability after single or repeated doses. Two patients, one with breast cancer and one with neuroendocrine tumor, experienced >30 % decrease in tumor size from baseline.

Conclusions

In Japanese patients with advanced cancer, single-agent abemaciclib has an acceptable safety profile and demonstrates antitumor activity at a dose of 200 mg Q12H. These findings support ongoing development of abemaciclib for diverse populations with advanced cancer.

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Titel: Phase 1 study of abemaciclib, an inhibitor of CDK 4 and 6, as a single agent for Japanese patients with advanced cancer
verfasst von: Yutaka Fujiwara
Kenji Tamura
Shunsuke Kondo
Yuko Tanabe
Satoru Iwasa
Akihiko Shimomura
Shigehisa Kitano
Ken Ogasawara
P. Kellie Turner
Joji Mori
Hiroya Asou
Edward Michael Chan
Noboru Yamamoto
Publikationsdatum: 16.06.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2016
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-3085-8

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Phase 1 study of abemaciclib, an inhibitor of CDK 4 and 6, as a single agent for Japanese patients with advanced cancer