A Study of HSK29116 in Adults With Relapsed/Refractory B-cell Malignancies
A Study of HSK29116 in Adults With Relapsed/Refractory B-cell Malignancies
This is a first-in-human Phase 1a/1b multicenter, open-label oncology study designed to
 evaluate the safety and anti-cancer activity of HSK29116 in patients with advanced B-cell
 malignancies.
This study is divided into 2 parts. Phase 1a is a dose escalation to evaluate the safety and
 tolerability of HSK29116 in adult patients with relapsed/refractory (R/R) B-cell
 malignancies, who have required and received at least 1 prior systemic therapy and for whom
 no other therapies are known to provide clinical benefit. Phase 1b will investigate the
 efficacy of HSK29116 at the dose selected in Phase 1a in up to 3 cohorts of patients with R/R
 B-cell malignancy indications who have received at least 1 prior systemic therapy, and at
 least half of the subjects must have received covalent BTK inhibitors who must have received
 genetic testing to get the mutation status of BTK C481 positive before enrollment：

 Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)； Mantle Cell Lymphoma
 (MCL)； Other B-cell malignancies (they will be selected according to the preliminary results
 of Phase Ia)
Inclusion Criteria:

 -  Males or females, of any race, aged ≥ 18 years.

 -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0- 2.

 -  Sufficient bone marrow function, hepatic function and Coagulation function.

 -  Patients must have measurable disease per disease-specific response criteria.

 -  Have histologically confirmed R/R CLL,SLL,MCL,Non-GCB DLBCL,FL(grade 1- 3a),MZL,WM.

 -  Received at least 1 prior systemic therapy(MCL no more than 5 lines of treatment) and
 have no other therapies known to provide clinical benefit.

 -  After the most recent treatment regimen, it is confirmed that PR has not been
 achieved, or there is confirmed progressive disease.

 -  Must require systemic therapy.

 -  The pregnancy test (urine or serum) of female subjects of childbearing potential shall
 be negative before enrollment.

 -  Female subjects of childbearing potential and fertile male subjects shall adopt one of
 the following highly effective contraception measures during the entire study and
 within 90 days after the study treatment is ended: abstinence, intrauterine device, or
 hormonal contraceptives beginning at least 3 months before the first dose of IMP.Male
 subjects are prohibited from donating sperm from the start of study treatment to 90
 days after the end of treatment.

 Exclusion Criteria:

 -  Subjects with central nervous system involvement.

 -  Subjects with histopathological transformation.

 -  Receipt of allogeneic hematopoietic stem cell transplantation ≤ 180 days before the
 start of study treatment administration on Cycle 1, Day 1, unless the subject is no
 longer on immunosuppressant medication. History of autologous hematopoietic stem cell
 transplantation within 12 weeks (84 days) before the start of study treatment.

 -  Continuous immunosuppressive therapy, including systemic (such as intravenous or oral)
 treatment with corticosteroids for the underlying diseases within 2 weeks before the
 first dose.

 -  Received any chemotherapy, biological therapy (such as monoclonal antibodies),
 immunotherapy, Chinese herbal medicines with anti-tumor efficacy, or other anti-tumor
 treatments within 4 weeks before the first use of HSK29116. The time interval from the
 last dose of BTK inhibitor or experimental small molecule drug to the first dose of
 the IMP is 5 times shorter than the half-life of the previously used drug.

 -  Previously developed toxicity due to anticancer treatment that did not resolve to
 Grade ≤ 1 (as per NCI-CTCAE 5.0), except for AEs not constituting a safety risk as
 assessed by the investigator.

 -  A history of other malignant tumors within 2 years before enrollment, except for basal
 cell carcinoma or skin squamous cell carcinoma having been adequately treated, or
 without disease for ≥ 2 years or with other types of cancer with the survival time of
 greater than 2 years. Subjects with breast or prostate cancer who are on maintenance
 hormonal therapies following therapeutic procedures with curative intent are
 permitted.

 -  Uncontrolled systemic active infections, or other infections or still on intravenous
 anti-infection treatment.

 -  Underwent major surgery in the past 4 weeks.

 -  Known infection with human immunodeficiency virus, or serologic status reflecting
 active hepatitis B or C infection.

 -  Subjects with severe cardiovascular diseases within 6 months before screening.

 -  Left Ventricular Ejection Fraction < 50% based on either echocardiogram or multigated
 acquisition (MUGA) scan.

 -  QTcF ≥ 450 msecs for males and QTcF ≥ 470 msec for females or other significant ECG
 abnormalities.

 -  Clinically significant gastrointestinal abnormalities that may affect the intake,
 transport, or absorption of drugs.

 -  Requiring or received anticoagulant therapy with warfarin or equivalent vitamin K
 antagonists (such as phenprocoumon) within 7 days before the first study treatment.

 -  Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura. Known
 history of bleeding diathesis.

 -  A history of stroke or intracranial hemorrhage within 6 months before the first study
 treatment.

 -  Use of CYP3A4 inhibitor or inducer within 7 days before the first study treatment, or
 using of sensitive substrates metabolized by CYP3A4/CYP2B6.