Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results

Shinya Rai, Won Seog Kim, Kiyoshi Ando, Ilseung Choi, Koji Izutsu, Norifumi Tsukamoto, Masahiro Yokoyama, Kunihiro Tsukasaki, Junya Kuroda, Jun Ando, Michihiro Hidaka, Youngil Koh, Hirohiko Shibayama, Toshiki Uchida, Deok Hwan Yang, Kenji Ishitsuka, Kenichi Ishizawa, Jin Seok Kim, Hong Ghi Lee, Hironobu Minami, Hyeon Seok Eom, Mitsutoshi Kurosawa, Jae Hoon Lee, Jong Seok Lee, Won Sik Lee, Hirokazu Nagai, Takero Shindo, Dok Hyun Yoon, Shinichiro Yoshida, Mireille Gillings, Hiroshi Onogi, Kensei Tobinai, Shinya Rai, Won Seog Kim, Kiyoshi Ando, Ilseung Choi, Koji Izutsu, Norifumi Tsukamoto, Masahiro Yokoyama, Kunihiro Tsukasaki, Junya Kuroda, Jun Ando, Michihiro Hidaka, Youngil Koh, Hirohiko Shibayama, Toshiki Uchida, Deok Hwan Yang, Kenji Ishitsuka, Kenichi Ishizawa, Jin Seok Kim, Hong Ghi Lee, Hironobu Minami, Hyeon Seok Eom, Mitsutoshi Kurosawa, Jae Hoon Lee, Jong Seok Lee, Won Sik Lee, Hirokazu Nagai, Takero Shindo, Dok Hyun Yoon, Shinichiro Yoshida, Mireille Gillings, Hiroshi Onogi, Kensei Tobinai

Abstract

Tucidinostat (formerly known as chidamide) is an orally available, novel benzamide class of histone deacetylase (HDAC) inhibitor that selectively blocks class I and class IIb HDAC. This multicenter phase IIb study aimed to investigate the efficacy and safety of tucidinostat, 40 mg twice per week (BIW), in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). The primary endpoint was overall response rate (ORR) assessed by an independent overall efficacy review committee. Between March 2017 and March 2019, 55 patients were treated, and 46 and 55 were evaluated for efficacy and safety, respectively. Twenty-one of 46 patients achieved objective responses with an ORR of 46% (95% confidence interval : 30.9-61.0), including five patients with complete response (CR). Responses were observed across various PTCL subtypes. In angioimmunoblastic T-cell lymphoma, there were two CR and five partial responses (PR) among eight patients, achieving an ORR of 88%. The disease control rate (CR + PR + stable disease) was 72% (33/46). The median progression-free survival, duration of response, and overall survival were 5.6 months, 11.5 months, 22.8 months, respectively. The most common adverse events (AE) (all grades) were thrombocytopenia, neutropenia, leukopenia, anemia, and diarrhea. The grade ≥3 AE emerging in ≥20% of patients included thrombocytopenia (51%), neutropenia (36%), lymphopenia (22%), and leukopenia (20%). Importantly, most of the AE were manageable by supportive care and dose modification. In conclusion, the favorable efficacy and safety profiles indicate that tucidinostat could be a new therapeutic option in patients with R/R PTCL (clinicaltrials gov. Identifier: NCT02953652).

Figures

Figure 1.
Figure 1.
Waterfall plot showing best percentage change from baseline in sum of products of perpendicular diameter of target lesions in 45 patients.
Figure 2.
Figure 2.
Swimmer plot showing treatment exposure and responses over time by peripheral T-cell lymphoma subtype in 46 pa- CI: 2.9-13.4) (Figure 3A), and the median DOR was 11.5 months (95% CI: 5.4-not reached [NR]) (Figure 3B). The median OS was 22.8 months (95% CI: 12.6-NR) (Figure 3C).
Figure 3.
Figure 3.
Durability of response to tucidinostat. (A) Kaplan-Meier plot of progression-free survival. (B) Kaplan-Meier plot of duration of response. (C) Kaplan-Meier plot of overall survival.

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