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A Phase I/II, Multicenter, Open-Label, Nonrandomized Study to Evaluate the Tolerability and Safety of ASTX660 and the Efficacy at the Recommended Dose of ASTX660 in Patients With Relapsed or Refractory T-Cell Lymphoma

A Phase I/II study of ASTX660 in patients with relapsed or refractory T-cell lymphoma

8

There were 3 female (37.5%) and 5 male (62.5%) subjects. The mean +- standard deviation age was 69.0 +- 9.8 years, and the mean +- standard deviation weight was 54.74 +- 10.27 kg. There were 7 subjects (87.5%) with an ECOG PS of 0 and 1 subject (12.5%) with an ECOG PS of 1. There were 7 subjects (87.5%) with PTCL and 1 subject (12.5%) with CTCL. Of these subjects, 8 subjects had received chemotherapy for the primary diagnosis, and 1 subject had received radiotherapy. None of them had undergone autologous hematopoietic stem cell transplantation for the primary diagnosis.

A total of 13 subjects were screened. Of these, 7 subjects were enrolled in cohort 1, which was to receive 120 mg of ASTX660 and 1 subject was enrolled in cohort 2, which was to receive 150 mg of ASTX660. All 8 subjects discontinued the administration of IMP and terminated their participation in the trial. Reasons for discontinuation of the IMP were progressive disease or disease relapse in 4 subjects, AEs in 2 subjects, and other reason in 1 subject in cohort 1, and progressive disease or disease relapse in 1 subject in cohort 2. Reasons for discontinuation of the trial were death in 4 subjects and other reasons in 3 subjects in cohort 1, and other reasons in 1 subject in cohort 2.

-The most common Treatment-emergent adverse events(TEAEs) included lymphopenia, amylase increased, lipase increased, and conjunctivitis. -No TEAEs leading to death or serious TEAEs were reported. -Treatment-emergent adverse events that led to the discontinuation of the IMP were reported in 2 subjects at 120 mg/day; these TEAEs were related to the IMP. -Grade 3 or higher TEAEs were reported in 4 subjects at 120 mg/day. No Grade 3 or higher TEAEs were reported at 150 mg/day.

Safety Results: -Dose-limiting toxicity reported in this trial included Grade 3 amylase increased in 1 subject at 120 mg/day. -ASTX660 administered orally in an intermittent (7 days on/7 days off) dosing regimen demonstrated a manageable safety profile and was tolerated at 120 mg/day.

Efficacy Results: -In cohort 1, 1 subject was assessed to be a responder and the Duration of response (DOR), Progression free survival (PFS), and Time to response (TTR) for the subject with PTCL, whose best overall response was partial response (PR), were 3 days, 33 days, and 31 days, respectively. -In cohort 1, 1 subject with PTCL had the longest PFS of 1184 days, with best overall response of stable disease. -There are limitations in explaining the efficacy of ASTX660 from the results obtained. Pharmacokinetic: The PK results following single and once daily oral administration of ASTX660 for cohort 1 (120 mg/day) and cohort 2 (150 mg/day) were as follows. The results in cohort 2 (150 mg) are based on the data from 1 subject; -On Cycle 1 Day 1, following single oral administration of ASTX660 at doses of 120 mg and 150 mg, the mean Cmax, AUC24h, and AUCt of ASTX660 all increased in a dose-dependent manner. -On Cycle 1 Day 1, the median tmax for 120 mg and 150 mg was 0.98 hours and 0.48 hours, respectively. -On Cycle 1 Day 7, the median tmax for 120 mg was 0.94 hours. -On Cycle 1 Day 7, the mean t1/2,z for 120 mg was 35.3 hours. -The mean accumulation ratios of Cycle 1 Day 7 to Cycle 1 Day 1 for Cmax, AUC24h, and Ctrough were 1.56, 1.88, and 2.96 for 120 mg, respectively.

-ASTX660 was generally tolerated at 120 mg/day in an intermittent (7 days on/7 days off) dosing regimens in Japanese subjects with r/r PTCL or r/r CTCL. -Dose-limiting toxicity reported in this trial included Grade 3 amylase increased in 1 subject at 120 mg/day. -No TEAEs leading to death or serious TEAEs were reported. -No significant safety concerns were identified in this trial, but the RD for the phase 2 part was not determined because the sponsor prematurely terminated the trial.

Sept. 25, 2025

No

Small studies with less than 25 participants are excluded from data sharing.

Otsuka Pharmaceutical Co., LTD.

2-16-4, Konan, Minato-ku, Tokyo, Japan

CL_OPCJ_RDA_Team@otsuka.jp

Otsuka Pharmaceutical Co., LTD.

2-16-4, Konan, Minato-ku, Tokyo, Japan

+81-3-6361-7314

opc_ctr@otsuka.jp

completed

May. 01, 2020

Interventional

multicenter, open-label, nonrandomized, phase 1/2 trial

treatment purpose

1-2

1) Patients with T-cell lymphoma with histological diagnosis based on WHO classification (2017)

2) Patients with evaluable lesions.

3) Patients with ECOG PS score of 0 or 1.

4) Patients with adequate organ functions as shown below.
a) AST and ALT 2.0xULN or less (3.0xULN or less if liver infiltration is present)
b) Total bilirubin 1.5xULN or less
c) ANC 1,000/mm3 or more (750/mm3 or more if bone marrow infiltration is present)
d) Platelet count 50,000/mm3 or more (25,000/mm3 or more if bone marrow infiltration is present)
e) Serum creatinine 1.5xULN or less or creatinine clearance 50 mL/min or more
f) Amylase and lipase 1.0xULN or less

1) Patients with active infection requiring treatment with antibiotics, antifungals, or antivirals

2) Patients with heart disease that meets the followings:
a) LVEF of < 50% by echocardiography or MUGA scan
b) Congestive heart failure (NYHA classification 3 or 4)
c) Uncontrolled heart disease including unstable angina pectoris or hypertension considered to require hospitalization within last 3 months (90 days)
d) Complete left bundle branch block, 3 degree (complete) atrioventricular block, use of pacemaker, history or complication of poorly controlled arrhythmia requiring treatment
e) History or complication of long QT syndrome
f) History or complication of ventricular arrhythmia requiring active treatment
g) Corrected QT interval of 470 or more msec based on 12-lead ECG performed at the screening
h) Concern on increased cardiac risk by participating in the study based on medical judgment

3) Patients receiving the following treatment for the primary disease prior to the initial dose of study drug
a) Chemotherapy or radiotherapy within last 3 weeks
b) Skin directed therapy including local treatment or phototherapy within last 3 weeks
c) Treatment with monoclonal antibody within last 4 weeks
d) Treatment with other study drugs or study treatment within last 3 weeks or 5 half-lives, whichever is longer

4) Patients with prior allogeneic stem cell transplantation, or autologous stem cell transplantation within 14 weeks prior to the day of initial dose of study drug

5) Patients who have received corticosteroids at a dose exceeding a prednisone equivalent dose of 10 mg/day within 3 weeks prior to the initial dose of study drug.

6) Patients with Inadequately controlled diabetes mellitus

Both

relapsed or refractory peripheral T-cell lymphoma(r/r PTCL),
relapsed or refractory cutaneous T-cell lymphoma(r/r CTCL),
relapsed or refractory adult T-cell leukemia/lymphoma(r/r ATLL)

investigational material(s)
Generic name etc : ASTX660
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Participants will receive ASTX660 monotherapy orally once daily (QD) from Day 1 to Day 7 and Day 15 to Day21 in 28 days cycle.


control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

safety
efficacy
Phase I part(dose-escalation part):Dose Limiting Toxicity,Safety
Phase I part(ATLL expansion part):Safety
Phase II part:Overall response rate(ORR)by the Central Data Review Committee

safety
efficacy
pharmacokinetics
pharmacodynamics
Phase I part (dose-escalation part and ATLL expansion part): Pharmacokinetics, Efficacy, pharmacodynamics

Phase II part: Efficacy, Safety, Pharmacokinetics

April. 06, 2020