A Phase I/II Study of ASTX660 in Patients With Relapsed or Refractory T-cell Lymphoma

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

Phase 1 (dose-escalation part): Investigate the tolerability and safety of ASTX660 in patients with r/r PTCL and r/r CTCL and determine the recommended dose (RD) for the Phase 2.

Phase 1 (ATLL expansion part): Evaluate the safety of ASTX660 at RD in patients with r/r ATLL.

Phase 2 : Evaluate the efficacy of ASTX660 at RD in patients with r/r PTCL.

Inclusion Criteria:

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.

   • AST and ALT ≤ 2.0 × ULN (≤ 3.0 × ULN if liver infiltration is present)
   • Total bilirubin ≤ 1.5 × ULN
   • ANC ≥ 1,000/mm3 (≥ 750/mm3 if bone marrow infiltration is present)
   • Platelet count 50,000/mm3 (25,000/mm3 if bone marrow infiltration is present)
   • Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min
   • Amylase and lipase ≤ 1.0 × ULN

Exclusion Criteria:

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

2. Patients with heart disease that meets the followings:

   1. LVEF of < 50% by echocardiography or MUGA scan
   2. Congestive heart failure (NYHA classification III or IV)
   3. Uncontrolled heart disease including unstable angina pectoris or hypertension considered to require hospitalization within last 3 months (90 days)
   4. Complete left bundle branch block, III degree (complete) atrioventricular block, use of pacemaker, history or complication of poorly controlled arrhythmia requiring treatment
   5. History or complication of long QT syndrome
   6. History or complication of ventricular arrhythmia requiring active treatment
   7. Corrected QT interval of ≥ 470 msec based on 12-lead ECG performed at the screening
   8. 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

   1. Chemotherapy or radiotherapy within last 3 weeks
   2. Skin directed therapy including local treatment or phototherapy within last 3 weeks
   3. Treatment with monoclonal antibody within last 4 weeks
   4. 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