TY - JOUR
T1 - Safety and antitumor activity of acalabrutinib for relapsed/refractory B-cell malignancies
T2 - A Japanese phase I study
AU - Izutsu, Koji
AU - Ando, Kiyoshi
AU - Ennishi, Daisuke
AU - Shibayama, Hirohiko
AU - Suzumiya, Junji
AU - Yamamoto, Kazuhito
AU - Ichikawa, Satoshi
AU - Kato, Koji
AU - Kumagai, Kyoya
AU - Patel, Priti
AU - Iizumi, Sakura
AU - Hayashi, Nobuya
AU - Kawasumi, Hisashi
AU - Murayama, Kosho
AU - Nagai, Hirokazu
N1 - Funding Information:
The study was funded by AstraZeneca. The authors would like to thank the patients, their families, and all the investigators involved in this study. We thank Sarah Bubeck, PhD, of Edanz Evidence Generation, for providing medical writing support, which was funded by AstraZeneca through EMC KK in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ).
Publisher Copyright:
© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2021/6
Y1 - 2021/6
N2 - This multicenter, open-label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B-cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three-part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty-five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment-related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression-free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well-tolerated in adult Japanese patients with B-cell malignancies.
AB - This multicenter, open-label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B-cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three-part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty-five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment-related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression-free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well-tolerated in adult Japanese patients with B-cell malignancies.
KW - Bruton's tyrosine kinase
KW - chronic lymphocytic leukemia
KW - mantle cell lymphoma
KW - pharmacokinetics
KW - small lymphocytic lymphoma
UR - http://www.scopus.com/inward/record.url?scp=85107322241&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107322241&partnerID=8YFLogxK
U2 - 10.1111/cas.14886
DO - 10.1111/cas.14886
M3 - Article
C2 - 33728735
AN - SCOPUS:85107322241
SN - 1347-9032
VL - 112
SP - 2405
EP - 2415
JO - Cancer Science
JF - Cancer Science
IS - 6
ER -
