A Study of BN102 in Patients With Previously Treated CLL/SLL and B-cell NHL

NCT ID: NCT05365100

Last Updated: 2023-03-24

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-31
• Study Completion Date: 2024-07-30

Brief Summary

This is a Multicenter Phase 1/2 Clinical Study to Evaluate the Safety and Efficacy of BN102 in Patients with Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and B-cell Non-Hodgkin's Lymphoma (NHL)

Detailed Description

The study is divided into 2 phases. Phase1 dose escalation part will enroll 17-36 patients to evaluate safety and tolerance of BN102 in patients with relapsed/refractory (R/R) CLL/SLL and B-NHL to determine maximum tolerated dose and recommended phase2 dose(RP2D).

Phase 2 expansion part will enroll 72-138 patients and be conducted at the selected dose level to further evaluate the safety and tolerability of BN102,as well as preliminary efficacy in specific subtypes of lymphoma. Patients will be allocated into 6 lymphoma subgroup cohorts depends on whether their previous treatment with or without BTK inhibitors.

• Cohort 1: patients with mantle cell lymphoma (MCL) previously treated with BTK inhibitors
• Cohort 2: patients with MCL who have not previously received a BTK inhibitor
• Cohort 3: patients with CLL/SLL who have received prior BTK inhibitors
• Cohort 4: patients with CLL/SLL who have not received prior BTK inhibitors
• Cohort 5: other B-NHL patients who have received prior BTK inhibitors
• Cohort 6: other B-NHL patients who have not received prior BTK inhibitors

Patients will receive orally administrated BN102 twice daily under fasting status. Study drug will be administered in 28-day cycles until disease progression or unacceptable toxicity, death, ICF withdraw ect. Subjects may receive study drug in the inpatient or outpatient setting.

Conditions

CLL/SLL; NHL

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase1dose escalation

Phase1 Dose Escalation Multiple dose levels of BN102 to be evaluated; determination of MTD/Phase 2 recommended dose(RP2D)

Group Type: EXPERIMENTAL

BN102

Intervention Type: DRUG

oral tablets: BN102, BID

Phase2 expansion in R/R MCL with BTK inhibitor treatment history

patients must have received at least one systemic treatment and failed or relapsed, patients previous treatment should with BTK inhibitor, approximate 12-23 patients this group

Group Type: EXPERIMENTAL

BN102

Intervention Type: DRUG

oral tablets: BN102, BID

Phase2 expansion in R/R MCL without BTK inhibitor treatment history

patients must have received at least one systemic treatment and failed or relapsed, patients previous treatment should without BTK inhibitor, approximate 12-23 patients this group

Group Type: EXPERIMENTAL

BN102

Intervention Type: DRUG

oral tablets: BN102, BID

Phase2 expansion in R/R CLL/SLL with BTK inhibitor treatment history

patients must have received at least one systemic treatment and failed or relapsed, patients previous treatment should with BTK inhibitor, approximate 12-23 patients this group

Group Type: EXPERIMENTAL

BN102

Intervention Type: DRUG

oral tablets: BN102, BID

Phase2 Expansion in R/R CLL/SLL without BTK inhibitor treatment history

patients must have received at least one systemic treatment and failed or relapsed, patents previous treatment should without BTK inhibitor, approximate 12-23 patients this group

Group Type: EXPERIMENTAL

BN102

Intervention Type: DRUG

oral tablets: BN102, BID

Phase2 Expansion in other R/R B-NHL with BTK inhibitor treatment history

patients must have received at least one systemic treatment and failed or relapsed, patents previous treatment should with BTK inhibitor, approximate 12-23 patients this group

Group Type: EXPERIMENTAL

BN102

Intervention Type: DRUG

oral tablets: BN102, BID

Phase2 Expansion in other R/R B-NHL without BTK inhibitor treatment history

patients must have received at least one systemic treatment and failed or relapsed, patents previous treatment should without BTK inhibitor, approximate 12-23 patients this group

Group Type: EXPERIMENTAL

BN102

Intervention Type: DRUG

oral tablets: BN102, BID

Interventions

BN102

oral tablets: BN102, BID

Intervention Type: DRUG

Other Intervention Names

AS-1763

Eligibility Criteria

Inclusion Criteria

All of the following conditions must be met for subject enrollment:

• Have fully understood and voluntarily signed the informed consent form ;
• Age ≥ 18 years;
• In phase 1, subjects with histologically confirmed CLL/SLL or B-cell NHL who are relapsed/refractory or intolerable after at least 1 prior line of adequate therapy, and have no better treatment choice as assessed by the investigator;
• In Phase 2, the 6 cohorts had the following specific enrollment criteria and required further treatment:
• Cohort 1: histologically confirmed MCL, failure or intolerance to at least one prior treatment including BTK inhibitor;
• Cohort 2: histologically confirmed MCL, failure or intolerance to at least 1 prior standard of care (BTK inhibitors naive);
• Cohort 3: histologically confirmed CLL/SLL, failure or intolerance to at least 1 prior treatment including BTK inhibitor;
• Cohort 4: histologically confirmed CLL/SLL, failure or intolerance to at least 1 prior standard of care (BTK inhibitors naive);
• Cohort 5: histologically confirmed other B-NHL, failure or intolerance to at least 1 prior treatment including BTK inhibitor;
• Cohort 6: histologically confirmed other B-NHL, failure or intolerance to at least 1 prior standard of care (BTK inhibitors naive);
• In addition to CLL and WM, subjects must have at least one radiographically measurable lesion
• ECOG score 0-2;
• Male or female patients of childbearing potential must agree to use effective methods of contraception

Exclusion Criteria

• Primary central nervous system lymphoma or lymphoma involving the central nervous system;
• Serological status reflects active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection
• HIV infection;
• Abnormalities in hematology lab results
• Cardiac, hepatic, renal, and coagulation abnormalities
• Concomitant clinically significant systemic active infection uncontrollable after appropriate antibiotics or other treatment;
• Expected survival of no more than 24 weeks as judged by the investigator;
• Major surgery within 4 weeks prior to the first dose of study drug
• Required or received anticoagulant therapy (warfarin, or equivalent vitamin K antagonist, or direct thrombin inhibitor, or factor Xa inhibitor, etc.) within 7 days prior to the first dose of study treatment;
• Had undergone cell transplantation or chimeric antigen receptor T cell (CAR-T) therapy within 60 days prior to enrollment
• Combined with uncontrolled active immune cytopenia
• Previous treatment with non-covalently binding BTK inhibitors (e.g. LOXO-305, MK-1026, etc.);
• Pregnant (positive pregnancy test at screening) or lactating female patients;
• QTcF > 450 msec in male patients or QTcF > 470 msec in female patients or other significant ECG abnormalities as judged by the investigator;
• Toxicities due to prior antilymphoma therapy have not stabilized and have not recovered to ≤ Grade 1 (except for clinically insignificant toxicities such as alopecia, etc.);
• History of other malignancies within 5 years prior to enrollment, special cases must be discussed with the medical monitor;
• Prior systemic anti-tumor therapy or investigational therapy received less than 4 weeks or 5 half-lives (whichever is shorter) from the start of the planned study treatment;
• Use of strong CYP3A inhibitors or inducers and proton pump inhibitors within 1 week or 5 half-lives (whichever is shorter) before administration of the first study drug;
• History of acute myocardial infarction, unstable angina, stroke, intracranial hemorrhage or transient ischemic attack within 6 months prior to enrollment; New York Heart Association (NYHA) grade 3 and 4 congestive heart failure;
• Live viral vaccination within 28 days prior to the first dose of study drug;
• Unable to take oral drugs, or have severe gastrointestinal diseases that investigator believes that it may affect the absorption of the study drug;
• Insufficient compliance of patients participating in this clinical study as judged by the investigator;
• Any other disease or condition in the judgment of the investigator that the patient is not suitable for the study drug, or will affect the interpretation of the study results

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioNova Pharmaceuticals (Shanghai) LTD.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Weili Zhao, Prof.

Role: PRINCIPAL_INVESTIGATOR

Shanghai Jiaotong University school of Medicine, Ruijin Hospital

Locations

ZhuJiang Hospital of Southern Medical University

Guangzhou, , China

The First Affiliated School of Guangxi Medical University

Nanning, , China

Shanghai Jiao Tong University School of Medicine, Ruijin Hospital

Shanghai, , China

The First Affiliated Hospital of Soochow University

Suzhou, , China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, , China

Henan Oncology Hospital

Zhengzhou, , China

Countries

China

Other Identifiers

BN102-101

Identifier Type: -

Identifier Source: org_study_id