Study of AXT-1003 in Adult Subjects With Relapsed/Refractory Non-Hodgkin Lymphomas

Inclusion Criteria:

1. Female or male subjects aged ≥ 18 years.

2. Histopathological diagnosis of relapsed/refractory non-Hodgkin lymphoma [R/R NHL] (except for CLL/SLL), who have progressed after treatment with approved therapies orwho have no access to approved or standard therapies. Note 1: Refractory is defined as failure to:

3. Achieve complete response after first-line therapy

4. Reach at least partial response after second-line therapy or beyond. Note 2:Subjects must be considered hematopoietic cell transplantation (HCT) ineligibleduring screening due to disease status (active disease), comorbidities, orother factors; the reason for HCT ineligibility must be clearly documented.

5. For dose expansion part: Subjects with pathologically confirmed R/R NHL by the localpathologist/investigators are enrolled. Most of the enrolled subjects are confirmedwith R/R PTCL subtype. Local histological diagnosis will be used for eligibilitydetermination. Subjects with PTCL are eligible according to 2016 World HealthOrganization (WHO) classification, including but not limited to the followingsubtypes:

6. PTCL, not otherwise specified.

7. Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) positive

8. Anaplastic large cell lymphoma, ALK negative

9. Angioimmunoblastic T-cell lymphoma

10. Extranodal NK-/T-cell lymphoma, nasal type The subjects enrolled in the doseexpansion part should be progressed after treatment with approved therapies orwho have no access to approved or standard therapies.

11. Eastern Cooperative Oncology Group performance status scale 0 to 1.

12. Have a life expectancy of at least 3 months.

13. Have measurable disease as defined by Lugano 2014 criteria, subjects must havemeasurable lesions (nodal lesion with any long diameter > 1.5 cm, or extranodallesion with any long diameter > 1.0 cm) (not mandatory for the dose escalationstage).

14. Willing to provide archived or fresh tumor tissue samples that are sufficient forEZH2 status detection (not mandatory).

15. Adequate organ function assessed within 7 days prior to study drug administration.

16. Bone marrow function: absolute neutrophil count (ANC) ≥ 1.0 × 109/L without growthfactor support (filgrastim or) for at least 14 days; Hb ≥ 9.0 g/dL (may receivetransfusion), platelets ≥ 75 × 109/L (Evaluated after at least 7 days since lastplatelet transfusion).

17. Hepatic function: serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) exceptfor unconjugated hyperbilirubinemia of Gilbert's syndrome; alkaline phosphatase (inthe absence of bone disease) ALT/AST ≤ 3.0 × ULN (≤ 5 × ULN if subject has livermetastases).

18. Renal function: calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gaultmethod).

19. Time between prior anticancer therapy and first dose of AXT-1003 as below:

20. Cytotoxic chemotherapy-at least 21 days or 3.5 half-lives of prior treatment,whichever occurs later.

21. Non-cytotoxic chemotherapy (eg, small molecule inhibitor)-at least 14 days or 3.5 half-lives of prior treatment, whichever occurs later.

22. Nitrosoureas-At least 6 weeks or 3.5 half-lives of prior treatment, whicheveroccurs later.

23. Monoclonal antibody (ies)-at least 28 days

24. Radiotherapy-At least 14 days from local site radiation therapy/at least 6weeks from prior radioisotope therapy/at least 12 weeks from 50% pelvic ortotal body irradiation.

25. High dose therapy with autologous hematopoietic cell infusion-at least 60 days.

26. High dose therapy with allogeneic transplant-At least 90 days (if graft versushost disease [GVHD] is present, must be Grade < 2) and no prohibitedmedications. Note: Starting at Cycle 1 Day 1, subjects may receive no more than 10 mg ofprednisone daily (or equivalent corticosteroid) when used for treatment of lymphomarelated symptoms, with the intent to taper by the end of Cycle 1.

27. Male subjects must have had a successful vasectomy (with confirmed azoospermia), orthey and their female partner must meet the criteria above (ie, not of childbearingpotential or practicing highly effective contraception and use a condom throughoutthe study period and for 3 months after study drug discontinuation).Non-vasectomized male subjects must also agree to refrain from donating sperm fromfirst dose of AXT-1003 until 3 months following the last dose of AXT-1003.

28. Females must not be lactating or pregnant at screening or baseline (as documented bya negative beta-human chorionic gonadotropin test with a minimum sensitivity of 25IU/L or equivalent units of beta-human chorionic gonadotropin). A separate baselineassessment is required if a negative screening pregnancy test was obtained more thanseven days before the first dose of study drug. All females will be considered aschildbearing potential unless they are postmenopausal (at least 12 monthsconsecutively amenorrheic, in the appropriate age group, and without other known orsuspected cause) or have been sterilized surgically (ie, bilateral tubal ligation,total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 monthbefore dosing). Females of childbearing potential must not have had unprotectedsexual intercourse within 30 days prior to study entry and must agree to use ahighly effective method of contraception, from the last menstrual period prior torandomization, during treatment cycles, and for 30 days (will be re estimated afterPK profile is known) after the final dose of study drug and have a male partner whouses a condom. Highly effective contraception includes:

29. Double barrier methods of contraception such as condom plus diaphragm orcervical/vault cap with spermicide.

30. Placement of an intrauterine device.

31. Established hormonal contraceptive methods: oral, injectable, or implant.Females who are using hormonal contraceptives must have been on a stable doseof the same hormonal contraceptive product for at least 4 weeks prior to dosingand must continue to use the same contraceptive during the study and for 30days after study drug discontinuation. Female subjects exempt from thisrequirement if they practice total abstinence or have a male partner who isvasectomized. If currently abstinent, the subject must agree to use a highlyeffective method of contraception as described above if they become sexuallyactive during the treatment cycles, and for 30 days after study drugdiscontinuation.

32. Signed ICF and willing to comply with all aspects of the protocol.

Exclusion Criteria:

1. Diagnosis of precursor B-cell lymphoblastic leukemia/lymphoma, precursor T-celllymphoblastic leukemia/lymphoma, precursor NK cell lymphoblastic leukemia/lymphoma.

2. Diagnosis of CLL, SLL.

3. Diagnosis of Burkitt lymphoma.

4. Received treatment with compounds with the same mechanism of action (EZH2 inhibitor,EZH1/EZH2 inhibitor etc.).

5. Central nervous system infiltration.

6. Clinically significant GVHD or GVHD requiring systemic immunosuppressive prophylaxisor treatment.

7. Uncontrolled or significant cardiovascular disease, including:

8. Evidence of prolongation of QT/QTc interval (eg, repeated episodes of QTcorrected for heart rate using Fridericia's method > 470 msec) (average oftriplicate determinations).

9. Diagnosed or suspected long QT syndrome or known family history of long QTsyndrome.

10. History of clinically relevant ventricular arrhythmias, such as ventriculartachycardia, ventricular fibrillation, or Torsade de Pointes.

11. Uncontrolled arrhythmia (subjects with asymptomatic, controllable atrialfibrillation may be enrolled) or asymptomatic persistent ventriculartachycardia.

12. History of second- or third-degree heart block. Subjects with a history ofheart block may be eligible if they currently have pacemakers and have nohistory of fainting or clinically relevant arrhythmia with pacemakers within 6months prior to screening.

13. Myocardial infarction within 6 months prior to screening.

14. Angioplasty or stent craft implantation within 6 months prior to screening.

15. Uncontrolled angina pectoris within 6 months prior to screening.

16. New York Heart Association Class 3 or 4 congestive heart failure.

17. Coronary/peripheral artery bypass graft within 6 months prior to screening.

18. Uncontrolled hypertension (resting systolic blood pressure > 160 mmHg ordiastolic blood pressure > 110 mmHg).

19. Complete left bundle branch block.

20. Venous thrombosis or pulmonary embolism within the last 3 months before startingtreatment.

21. Major surgery within 4 weeks before the first dose of study drug. Note: Minorsurgery (e.g, minor biopsy of extracranial site, central venous catheter placement,shunt revision) is permitted within 3 weeks prior to enrolment.

22. Known or suspected hypersensitivity to AXT-1003 or any of the excipients.

23. Inability to take oral medication, or malabsorption syndrome or any otheruncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) thatmight impair the bioavailability of AXT-1003.

24. Use of known median or potent Cytochrome P450 3A4 (CYP3A4) inducers/inhibitors or Pglycoprotein (P-gp) inhibitors.

25. Subjects unwilling to remove seville oranges, grapefruit juice and grapefruit fromtheir diet.

26. History of other malignancies prior to enrolment; except for subjects with basalcell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ,or other carcinomas in situ who have undergone possible curative treatment and donot have disease recurrence within 5 years since starting the treatment.

27. Any prior treatment-related (ie, chemotherapy, immunotherapy, radiotherapy, targettherapy or other study clinical therapy) clinically significant toxicities that havenot resolved to Grade ≤ 1 per CTCAE version 5.0 or prior treatment-relatedtoxicities that are clinically unstable and clinically significant at time ofenrolment.

28. Active infection requiring systemic therapy.

29. Has known history of chronic infection with hepatitis B virus (hepatitis B surfaceantigen positive) or hepatitis C virus (detectable antihepatitic C circulating viralRNA).

30. Immunocompromised subjects, including subjects known to be infected with humanimmunodeficiency virus, and tuberculosis.

31. Females who are pregnant or breastfeeding.

32. Any other major illness that, in the investigator's judgment, will substantiallyincrease the risk associated with the subject's participation in this study.