Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Male or female subjects ≥18 years of age;
Willing and able to understand and sign an informed consent form and to comply with all aspects of the protocol;
Life expectancy of ≥12 weeks;
Eastern Cooperative Oncology Group (ECOG) performance status 0-2;

Histologically confirmed B-cell Malignancies who have relapsed or are refractory to standard of care therapies, and have received ≥1 prior lines of therapy:

Part A: Subjects with B-cell Malignancies (regardless of subtype); Part B: Subjects With Selected Relapsed/Refractory B-cell Malignancies based on data from Part A;

There must be radiographically measurable disease for effects assess at dose expansion cohort;

Adequate organ function, as specified below:

Hematologic: Platelet count >65 × 10^9/L (may be posttransfusion, must one week before the first dose of starting study treatment); Hemoglobin (Hgb) ≥ 80 g/L; international normalized ratio (INR) or plasma prothrombin time (PT) ≤1.5 × ULN; absolute neutrophil count >1.0 × 10^9/L (growth factor use is allowed to bring pre-treatment neutrophils to >1.0 × 10^9 cells/L if bone marrow infiltration is involved, provided this is not within 7 days of starting study treatment); Hepatic: Total bilirubin <1.5 × upper limit normal (ULN), Total bilirubin <3 × ULN for Gilbert Syndrome; Aspartate aminotransferase (AST) and Alanine transaminase (ALT) ≤2.5 × ULN; Renal: Creatinine clearance ≥60 mL/min (as estimated by the Cockcroft-Gault equation );

Willing to have bone marrow biopsy/aspirate for baseline disease assessment and assessment of response to treatment;
Willingness of men and women of reproductive potential to observe conventional and highly effective birth control from the beginning of the study screening until 6 months after receiving the last treatment of investigational product. A fertile woman must be confirmed by a positive serum beta-human chorionic gonadotropin [β-hCG] test before 7 days of starting study treatment.

Exclusion Criteria:

History of other active malignancies within 1 years of study entry, with the exception of adequately treated in-situ carcinoma of cervix, localized basal cell or squamous cell carcinoma of skin, previous malignancy that was not recurred in 5 years;
History of allogeneic or autologous stem cell transplant or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 100 days before starting study treatment, or diagnosis of graft vs host disease;
Clinically significant, uncontrolled cardiac or cardiovascular disease, or history of myocardial infarction, New York Heart Association (NYHA) Class III or IV, QTc prolongation (defined as a QTc > 450 ms) or other significant electrocardiogram (ECG) abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) ,within 6 months prior to planned start of MH048 treatment;
Transformation (e.g., Richter's transformation, prolymphocytic leukemia, or blastoid lymphoma) prior to the planned start of MH048 treatment;
Subjects with known or suspected history of allergy to MH048 capsules or excipients;
Any unresolved toxicities from prior therapy of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v5.0) Grade 2 or higher at the time of starting MH048 treatment, with the exception of toxicities not considered a safety risk (eg, alopecia, neuropathy, or asymptomatic laboratory abnormalities);
Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection;
Active uncontrolled autoimmune disease;
Clinically significant active malabsorption syndrome;
Subjects with human immunodeficiency virus (HIV) , Active hepatitis B virus (HBsAg positive, or HBsAg negative/HBcAb positive ，and HBV DNA>10^3) or Active HCV infection (HCVAb positive ,and HCV RNA positive);
Major surgery within 4 weeks prior to planned start of MH048 treatment (expect for biopsy, laser eye surgery)；
Women of childbearing potential who are pregnant or lactating;
Subjects requiring therapeutic anticoagulation;
Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of MH048 treatment;
Received a CYP3A4, CYP2A8 strong inhibitor or inducer within 5 half-lives of planned investigational product administration；
Medical history of massive bleeding (hemophilia or other disease need the treatment of blood transfusion）;
Severe neurological/mental illness, and in the opinion of the Investigator, is unable to adhere to the requirements of the study;
Receipt of any investigational agent or clinical study within 28 days;
Unstable brain metastasis patient.