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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04861779




Registration number
NCT04861779
Ethics application status
Date submitted
20/04/2021
Date registered
27/04/2021
Date last updated
3/08/2022

Titles & IDs
Public title
A Study of HSK29116 in Adults With Relapsed/Refractory B-cell Malignancies
Scientific 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
Secondary ID [1] 0 0
HSK29116-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory B-Cell Malignancies 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HSK29116

Experimental: Phase 1a Dose Escalation - Multiple dose levels of HSK29116 to be evaluated; determination of MTD/Phase 1b recommended dose

Experimental: Phase 1b Dose Expansion in R/R CLL or SLL - 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.

Experimental: Phase 1b Dose Expansion in R/R MCL - 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.

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


Treatment: Drugs: HSK29116
Oral HSK29116
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Protocol Specified Dose-Limiting Toxicities
Timepoint [1] 0 0
1 year
Primary outcome [2] 0 0
To establish the MTD and/or recommended Phase 1b dose of HSK29116
Timepoint [2] 0 0
1 year
Primary outcome [3] 0 0
Number of Participants with Adverse Events and Clinical Laboratory Abnormalities
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Pharmacokinetic(PK) Profile of HSK29116: Maximum Serum Concentration
Timepoint [1] 0 0
At the end of Cycle 1 (each cycle is 28 days)
Secondary outcome [2] 0 0
Overall response rate(ORR) as assessed by the Investigator
Timepoint [2] 0 0
Up to 3 Years
Secondary outcome [3] 0 0
Duration of response(DoR) as assessed by the Investigator
Timepoint [3] 0 0
Up to 3 Years
Secondary outcome [4] 0 0
Progression-free survival(PFS) as assessed by the Investigator
Timepoint [4] 0 0
Up to 3 Years
Secondary outcome [5] 0 0
Time to response(TTR) as assessed by the Investigator
Timepoint [5] 0 0
Up to 3 Years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2023
Actual
Sample size
Target
156
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
One Clinical Research - Perth
Recruitment postcode(s) [1] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
China
State/province [1] 0 0
Guangdong
Country [2] 0 0
China
State/province [2] 0 0
Henan
Country [3] 0 0
China
State/province [3] 0 0
Hunan
Country [4] 0 0
China
State/province [4] 0 0
Jiangsu
Country [5] 0 0
China
State/province [5] 0 0
Shandong
Country [6] 0 0
China
State/province [6] 0 0
Zhejiang

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Haisco Pharmaceutical Group Co., Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04861779
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Shufang Zhang
Address 0 0
Haisco Pharmaceutical Group Co., Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Xue Gu
Address 0 0
Country 0 0
Phone 0 0
86-13840370891
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04861779