A Study to Evaluate Activity, Safety and Tolerability of ZX-101A in Relapsed/Refractory Hematological Malignancies

Inclusion Criteria:

• Males and females who are ≥ 18 years old

• Minimum life expectancy ≥ 3 months (determined by investigator assessment)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to1.

• Histopathological and cytological confirmed diagnosis of hematological malignancies.

• Phase I dose expansion and phase II studies require at least 1 measurable lesion,including cutaneous T-cell lymphoma [CTCL] without evidence of skin involvement.

• Acceptable bone marrow function.

• Acceptable organ function: creatinine clearance ≥ 60 mL/min calculated according toinstitutional standard practice assessment (according to the Cockcroft-Gaultformula) for kidney function; AST and ALT ≤ 2.5 x upper limit of normal (ULN) (ASTand ALT ≤ 4 x ULN in subjects with liver involvement); total bilirubin ≤ 1.5 x ULN (total bilirubin ≤ 3 in subjects with Gilbert syndrome ×ULN) for liver function.

• No transfusion or cytokine support for ≥ 2 weeks before first dosing.

• Ability to swallow oral medication.

• Negative serum pregnancy test in women of childbearing potential at screening.

• Females of childbearing potential and males with female partners of childbearingpotential must agree to use effective contraception during the study period and for 6 months (females) or 3 months (males) after the last dose of ZX-101A.

• Men must agree to no sperm donation during the study and for 3 months after the lastdose of ZX-101A.

• Understands the requirements of the study, is willing to comply with all studyprocedures and signed the IRB-approved informed consent.

Exclusion Criteria:

• Previous use of PI3K δ/γ dual inhibitors

• Received approved anti-cancer drugs within 28 days (42 days for nitrosoureas) or 5half-lives, whichever is longer.

• Radiation treatment within 2 weeks prior to first dose of study treatment.

• Received investigational study drug within 28 days (or 5 half-lives, whichever islonger).

• Received organ transplantation in the past (hematopoietic stem cell transplantationin the past is allowed).

• Major surgery within 28 days prior to the first dose of study drug

• Has not recovered from adverse events from prior anti-cancer treatment (withexception of alopecia).

• Concurrent participation in another therapeutic treatment trial.

• Those who have been vaccinated with live vaccines or live attenuated vaccines within 30 days before the first administration, and seasonal influenza vaccines withoutlive viruses are allowed.

• Received warfarin or factor Xa inhibitor within 5 half-lives before the first doseof study drug.

• With central nervous system (CNS) involvement or active leptomeningeal disease.

• History of other malignancy within the past 5 years, unless cured by surgery andsustained disease-free survival.

• CLL with Richter transformation.

• Active autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)

• Chronic immunosuppression conditions.

• QTcF interval > 480 msec; echocardiographic detection of left ventricular ejectionfraction < 45%.

• Uncontrolled systemic diseases, including myocardial infarction or bypass, stentsurgery, or other heart disease, in the judgement of the investigator, inappropriatefor enrollment.

• Active uncontrolled infection within 14 days before first dosing.

• Active infection of Hepatitis B virus or hepatitis C virus; history of HIVinfection.

• History of drug-induced liver injury, chronic active hepatitis, alcoholic liverdisease, nonalcoholic steatohepatitis, primary biliary cirrhosis, persistentextrahepatic obstruction due to gallstones, cirrhosis or portal vein history ofhypertension.

• History of interstitial lung disease, hypersensitivity pneumonitis, pulmonaryfibrosis, radiation pneumonitis and severe pulmonary function impairment, or otherpulmonary diseases that significantly affect the safety or compliance of patientsafter being evaluated and included by the investigator.

• Gastrointestinal dysfunction, including motility or malabsorption syndromes orinflammatory bowel disease which could limit absorption of study drug.

• Any concurrent uncontrolled illness, including mental illness or substance abuse.