Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)

Phase 2b, open-label, non-randomized, single arm study to evaluate the safety, efficacy, and pharmacokinetics of HBI-8000 40 mg BIW in patients with relapsed or refractory PTCL (R/R PTCL).

This is a Phase 2b, open-label, non-randomized, single arm study to evaluate the safety, efficacy, and pharmacokinetics of HBI-8000 40 mg BIW in patients with relapsed or refractory PTCL (R/R PTCL). HBI 8000 will be administered orally approximately 30 minutes after any regular meal twice a week. There will be 3-4 days between dosing. A cycle is defined as consecutive 28 days. HBI-8000 administration will be continued until disease progression or unacceptable toxicities are observed despite appropriate dose reduction or treatment interruption.

Eligibility Criteria:
Inclusion Criteria:

1. Histological or cytological diagnosis of the following peripheral T-cell lymphoma (PTCL) subtypes as defined by the WHO classification (2008) may be included:

   1. PTCL, NOS
   2. Angioimmunoblastic T-cell lymphoma (AITL)
   3. Anaplastic large-cell lymphoma (ALCL), ALK+
   4. Anaplastic large-cell lymphoma (ALCL), ALK-
   5. Enteropathy-associated T-cell lymphoma (EATL)
   6. Hepatosplenic T-cell lymphoma
   7. Subcutaneous panniculitis-like T-cell lymphoma
2. Patients for whom at least 1 measurable lesion is confirmed by the lesion assessment at baseline; an evaluable lesion is defined as more than 1.5 cm in greatest dimension and can be followed by imaging.
3. Relapsed or refractory disease after receiving ≥1 prior systemic therapy with antitumor agent(s) and there is no other available treatment which can be considered appropriate for patients. Systemic therapy is defined as frontline chemotherapy or immunotherapy administered systemically.
4. Male or female, age 20 years or older
5. ECOG Performance Status of 0-2
6. Life expectancy of greater than 3 months
7. Meeting the following laboratory criteria for screening:

   1. Absolute Neutrophil Count \>1500/µL independent of growth factor support within 7 days of starting the study drug
   2. Platelets \>75,000/µL independent of transfusion within 14 days of starting the study drug
   3. Hgb \>8 g/dL independent of transfusion within 14 days of starting the study drug
   4. Serum creatinine \< 1.5 X ULN
   5. Serum aspartate aminotransferase/glutamyl oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/glutamyl pyruvic transaminase (ALT/SGPT) less than or equal to 3 X ULN
   6. Serum Bilirubin less than or equal to 1.5 X ULN
8. Negative serum pregnancy test for females of childbearing (reproductive) potential. Female patients of child bearing potential must use an effective method of birth control (e.g., hormonal contraceptive, intrauterine device, diaphragm with spermicide or condom with spermicide) during treatment period and 1 month thereafter. Males must use an effective method of birth control (2 barrier methods) during treatment period and 3 months thereafter.

   Note: Female patients will be considered to be women of childbearing potential unless having undergone permanent contraception or postmenopausal. Postmenopausal is defined as at least 12 months without menses with no other medical reasons (e.g., chemical menopause because of treatment with anti-malignant tumor agents)
9. Signed informed consent

Exclusion Criteria:

1. Patients in whom central nervous system lymphoma is recognized during screening (if suspected clinically, imaging study should be performed to confirm)
2. Male patients with QTcF \> 450 msec at screening, female patients with QTcF \> 470 msec at screening or patients with congenital long QT syndrome, clinically significant arrhythmia, history of congestive heart failure (New York Heart Association Class III or IV) or acute myocardial infarction within 6 months of starting the study drug
3. Patients with known hypersensitivity to benzamide class of compounds or any of the components of HBI-8000 tablets, and patients with prior exposure of HBI-8000
4. Patients with a history of second malignancy other than disease under study. The exceptions are disease that has been treated with curative intent with no evidence of recurrence in past 2 years including:

   1. Basal cell carcinoma of the skin
   2. Squamous cell carcinoma of the skin
   3. Cervical carcinoma in situ
   4. Carcinoma in situ of the breast
   5. An incidental histological finding of prostate carcinoma (TNM stage T1a or T1b)
   6. Early-stage gastric cancer treated with endoscopic mucosal resection or endoscopic submucosal dissection
   7. Thyroid cancer with differentiated histology (e.g. papillary) treated with curative intent
5. Autologous stem cell transplantation within 12 weeks (84 days) of starting the study drug
6. History of allogeneic stem cell transplantation
7. Organ transplantation recipients except autologous hematopoietic stem cell transplantation
8. Uncontrolled inter-current infection
9. Hepatitis B surface antigen-positive, or hepatitis C virus antibody positive. In case hepatitis B core antibody and/or hepatitis B surface antibody is positive even if hepatitis B surface antigen-negative, a hepatitis B virus DNA test (real-time PCR measurement) should be performed and if positive, the patient should be excluded from study
10. Any history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
11. Uncontrolled diabetes mellitus, hypertension, endocrine disorder, bleeding disorder
12. Major surgery or radiation therapy within 28 days of starting the study drug
13. Receiving investigational agents or anti-cancer therapy, within 28 days, nitrosourea or mitomycin C within 42 days of starting the study drug
14. Receiving antibody therapy for PTCL within 12 weeks of starting the study drug
15. Women who are breastfeeding or women who are not willing to stop breastfeeding during study treatment period and for 30 days after the last dose of study drug
16. Potential for non-compliance or at increased risk based on investigator's judgement