Phase Ib Clinical Study of Keynatinib

NCT04807881 | Recruiting Phase 1

• 1 other identifier: MEDO-BTK-20001
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, PK characteristics in subjects with relapsed/refractory B-cell lymphoma. Furthermore, the relationship between the exposure level of Keynatinib and its efficacy and safety, the penetration rate of keynatinib in the Blood-Brain Barrier (BBB) and its PK characteristics in cerebrospinal fluid in R/R-PCNSL patients, the relationship between the BTK receptor occupancy rate and the efficacy are also evaluated.

Conditions

Lymphoma, B-Cell

Keywords

Relapsed/Refractory Primary Central Nervous System Lymphoma; Relapsed/Refractory Chronic Lymphoblastic Leukemia; Relapsed/Refractory Small Lymphocytic Lymphoma; Relapsed/Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (CR+PR)

  The proportion of subjects whose optimal efficacy observed from the beginning of administration is CR or PR.

  Every 2 administration cycles in cycle 1-6 and every 3 administration cycles in cycle 7-n.

Study Arms (1)

Keynatinib treatment group

EXPERIMENTAL

Keynatinib, 20 mg，BID

Drug: Keynatinib

Interventions

Keynatinib DRUG

All subjects shall be treated with Keynatinib twice a day (once every 12 hours), 20 mg each time, fasting within 2 hours before and 1 hour after taking the drug, and taking warm water when taking the drug. It is recommended to take the drug at the same time every day. In case of missed administration, the subjects should be instructed to take it as soon as possible when they think of it on the same day. If it is within 3 hours later than the scheduled administration, the study drug should be taken as soon as possible; if the interval is \> 3 hours, skip this time and take the next dose at the normal scheduled time. Do not take double dose at one time. Every 28 days is a treatment cycle until the specified interview completed, PD, intolerable toxicity, death occurs or withdraw from the study (including withdrawal of informed consent by the subject or termination of the study when the investigator judges that the risk is greater than the benefit), whichever occurs first.

Also known as: TL007

Keynatinib treatment group

Eligibility Criteria

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

You may qualify if:

• Unlimited gender, age ≥ 18 years (including critical value)-Cohort 1/2/3;
• Voluntarily participate in the study and sign the ICF, follow the trial treatment protocol and interview plan-Cohort 1/2/3;
• The subject's disease diagnosis meets all of the following conditions:
• Cohort 1:
• Primary central nervous system lymphoma (PCNSL) confirmed by pathology;
• For relapsed or refractory PCNSL, at least first line treatment must be given to Central Nervous System (CNS) lesions;
• Brain Magnatic resonance Imaging (MRI) or Computerized tomography (CT) shows solid lesions of PD;
• Cohort 2:
• CLL/SLL diagnosed according to IWCLL 2008 standards;
• Refractory or relapsed CLL/SLL that previously received at least first-line systemic treatment. First-line treatment is defined as at least 2 cycles of standard protocol or clinical trial research protocol completed based on current guidelines;
• Accord with at least one indication of CLL / SLL that requiring treatment;
• There is medical record confirming that it is invalid or Progression Disease occurs after response for the latest treatment;
• CT /MRI shows measurable lesions, which is defined as at least one lymph node with a maximum axis of more than 1.5 cm and with 2 measurable vertical dimension;
• It is allowed to include the patients with a stable condition involving the central nervous system;
• Cohort 3:

You may not qualify if:

• Cohort 1: R/R-PCNSL
• PCNSL is pathologically diagnosed as T-cell lymphoma;
• Have previously received any of the following treatments:
• Chemotherapy, targeted therapy, radiotherapy or antibody based anti-tumor therapy are used within 4 weeks before the first administration or within 5 half-lives (whichever is shorter);
• Have previously received the treatment of B Cell Receptor (BCR) inhibitors (such as BTK, phosphoinositide kinase 3 kinase \[PI3K\] or SYK inhibitors) or BCL-2 inhibitors (such as ABT-199) or Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) or a bispecific antibody drug;
• Have received Allogenetic Haematopoietic Stem Cell Transplantation (Allo-HSCT) or other organ transplants (except for those who have received ASCT more than six months);
• Take ≥ 8 mg dexamethasone or equivalent daily to control lymphoma symptoms;
• CNS external beam radiotherapy within 21 days before the first administration;
• The systemic immunosuppressants, including cyclosporine A, tacrolimus, sirolimus and other drugs, haven't stopped 28 days before the first use of the study drug, or \> 5 mg/day of prednisone or its equivalent has been taken for long period;
• Have other malignant tumors within 3 years, except for the curable basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of cervix or breast;
• Non-hematologic toxicity of the previous anti-tumor treatment has not recovered to ≤ grade 1 (except for hair loss);
• Have uncontrollable or severe cardiovascular disease, including:
• Congestive heart failure with New York Heart Association (NYHA) grade II or higher, unstable angina, myocardial infarction within 6 months before first study drug administration, or arrhythmia requiring treatment during screening, Left Ventricular Ejection Fraction (LVEF) \<50% ;
• Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, and atypical cardiomyopathy);
• Clinically significant QTc interval prolonged medical history, or the QTc interval of screening period \> 470 ms in female, and \> 450 ms in male;

Sponsors & Collaborators

• Medolution Ltd.: lead

Study Sites (4)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

NOT YET RECRUITING

Peking University Third Hospital

Beijing, Beijing Municipality, 100083, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

West China Hospital，Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell; Recurrence; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease

Study Officials

• Dawei Zhang, phD

  Medolution Ltd.

  STUDY DIRECTOR

Central Study Contacts

Jin Yan, MD

CONTACT

+8618652596381; jin.yan@teligene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 19, 2021
• Study Start: September 24, 2020
• Primary Completion (Estimated): October 10, 2027
• Study Completion (Estimated): April 10, 2028
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)