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

NCT04861779 | Unknown Phase 1

• 1 other identifier: HSK29116-101
• Study Type: interventional
• Target: 156
• Locations: 2 countries
• Sites: 8

Brief 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.

Conditions

Relapsed/Refractory B-Cell Malignancies

Outcome Measures

Primary Outcomes (3)

• Number of Participants with Protocol Specified Dose-Limiting Toxicities

  Phase 1a

  1 year

• To establish the MTD and/or recommended Phase 1b dose of HSK29116

  Phase 1a

  1 year

• Number of Participants with Adverse Events and Clinical Laboratory Abnormalities

  Phase 1a/1b

  Up to 3 years

Secondary Outcomes (5)

• Pharmacokinetic(PK) Profile of HSK29116: Maximum Serum Concentration

  At the end of Cycle 1 (each cycle is 28 days)

• Overall response rate(ORR) as assessed by the Investigator

  Up to 3 Years

• Duration of response(DoR) as assessed by the Investigator

  Up to 3 Years

• Progression-free survival(PFS) as assessed by the Investigator

  Up to 3 Years

• Time to response(TTR) as assessed by the Investigator

  Up to 3 Years

Study Arms (4)

Phase 1a Dose Escalation

EXPERIMENTAL

Multiple dose levels of HSK29116 to be evaluated; determination of MTD/Phase 1b recommended dose

Drug: HSK29116

Phase 1b Dose Expansion in R/R CLL or SLL

EXPERIMENTAL

CLL/SLL patients must have received at least one systemic treatment and failed or relapsed, of which at least half of the subjects must have received covalent BTK inhibitors and have BTK C481 mutation.

Drug: HSK29116

Phase 1b Dose Expansion in R/R MCL

EXPERIMENTAL

MCL patients must have received at least one systemic treatment and failed or relapsed, of which at least half of the subjects must have received covalent BTK inhibitors and have BTK C481 mutation.

Drug: HSK29116

Phase 1b Dose Expansion in other R/R B-cell Malignancy

EXPERIMENTAL

Patients must have received at least one systemic treatment and failed or relapsed, of which at least half of the subjects must have received covalent BTK inhibitors and have BTK C481 mutation.

Drug: HSK29116

Interventions

HSK29116 DRUG

Oral HSK29116

Phase 1a Dose Escalation; Phase 1b Dose Expansion in R/R CLL or SLL; Phase 1b Dose Expansion in R/R MCL; Phase 1b Dose Expansion in other R/R B-cell Malignancy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (8)

One Clinical Research

Perth, Australia

NOT YET RECRUITING

NANFANG Hospital

Guangzhou, Guangdong, China

NOT YET RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

RECRUITING

Hunan Cancer Hospita

Changsha, Hunan, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, China

NOT YET RECRUITING

Shandong Provincial Hospital

Jinan, Shandong, China

NOT YET RECRUITING

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

NOT YET RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hanzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Shufang Zhang

  Haisco Pharmaceutical Group Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Xue Gu

CONTACT

86-13840370891; gux@haisco.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: April 27, 2021
• Study Start: August 24, 2021
• Primary Completion: August 1, 2023
• Study Completion: October 1, 2023
• Last Updated: August 3, 2022

Record last verified: 2022-08

Locations

CN (7); AU (1)