A Study of HSK29116 in Adults With Relapsed/Refractory B-cell Malignancies

Relapsed/Refractory B-Cell Malignancies Clinical Trial

Official title:

A Phase Ia/b Clinical Study on Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of BTK Protein Degradation Agent HSK29116 in Subjects With Relapsed or Refractory B-Cell Malignancy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04861779
• Other study ID #: HSK29116-101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 24, 2021
• Est. completion date: October 2023

Study information

• Verified date: August 2022
• Source: Haisco Pharmaceutical Group Co., Ltd.
• Contact: Xue Gu
• Phone: 86-13840370891
• Email: gux[@]haisco.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 2 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 2 prior systemic therapy： 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 156
• Est. completion date: October 2023
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 2 prior systemic therapy 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.
• Patients who have received BTKis, tyrosine kinase inhibitors or other targeted small molecule drugs for anti-tumor treatment within 7 days (or 5 half-lives, whichever is shorter) before initiation of study drug; or patients who have received any biological and/or immune-based anti-tumor treatment, including investigational treatment (including but not limited to monoclonal antibody therapy and/or anti-tumor vaccine) within 4 weeks (or 5 half-lives, whichever is shorter); or patients who have received systemic chemotherapy, radiotherapy or traditional Chinese medicines with anti-tumor effect (traditional Chinese medicines with anti-tumor indications specified in the package insert) within 2 weeks (or 5 half-lives, whichever is shorter).
• 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.

Related Conditions & MeSH terms

• Neoplasms
• Relapsed/Refractory B-Cell Malignancies

Intervention

Drug:
• HSK29116
Oral HSK29116

Locations

Country	Name	City	State
Australia	One Clinical Research	Perth
China	Hunan Cancer Hospita	Changsha	Hunan
China	NANFANG Hospital	Guangzhou	Guangdong
China	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hanzhou	Zhejiang
China	Shandong Provincial Hospital	Jinan	Shandong
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Haisco Pharmaceutical Group Co., Ltd.

Countries where clinical trial is conducted

Australia,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Protocol Specified Dose-Limiting Toxicities	Phase 1a	1 year
Primary	To establish the MTD and/or recommended Phase 1b dose of HSK29116	Phase 1a	1 year
Primary	Number of Participants with Adverse Events and Clinical Laboratory Abnormalities	Phase 1a/1b	Up to 3 years
Secondary	Pharmacokinetic(PK) Profile of HSK29116: Maximum Serum Concentration	Phase1a/1b-Sampling of the first dose, pre and post-dose at selected cycle	At the end of Cycle 1 (each cycle is 28 days)
Secondary	Overall response rate(ORR) as assessed by the Investigator	Phase 1a/1b	Up to 3 Years
Secondary	Duration of response(DoR) as assessed by the Investigator	Phase 1a/1b	Up to 3 Years
Secondary	Progression-free survival(PFS) as assessed by the Investigator	Phase 1a/1b	Up to 3 Years
Secondary	Time to response(TTR) as assessed by the Investigator	Phase 1a/1b	Up to 3 Years