Phase I/IIa Study of BR1733 in Subjects With Advanced Cancers

Phase 1

Active, not recruiting

• Conditions: Advanced Cancer; Follicular Lymphoma; Peripheral T Cell Lymphoma; Diffuse Large B Cell Lymphoma
• Interventions: Drug: BR1733

• Registration Number: NCT05749549
• Lead Sponsor: Shanghai Blueray Biopharma Co., Ltd.

Brief Summary

This study is a Phase I/IIa, multi-center, open-label study of BR1733 with a dose escalation part followed by a dose expansion part in adult subjects with advanced cancers.

This treatment to characterize the safety, tolerability, PK, PD and preliminary antitumor activity.

The study treatment will be administered until the subject experiences unacceptable toxicity, progressive disease, and/or has treatment discontinued at the discretion of the Investigator or the subject, or due to withdrawal of consent.

Detailed Description

This is a multi-center, nonrandomized, open-label study to evaluate the safety, tolerability, pharmacokinetics/ pharmacodynamics, and efficacy of BR1733 in patients with advance cancer, such as recurrent/refractory follicular lymphoma, peripheral T cell lymphoma(PTCL), diffuse large B cell lymphoma(DLBCL) and advance solid tumors.

Phase Ⅰ (Dose Escalation Phase): According to the incidence of DLT in BR1733 tablets in the treatment of advanced cancers, MTD and the Phase 2 clinical trial dose (RP2D) combining PK, PD, efficacy and safety data were determined.

Phase IIa (Dose expansion stage): Evaluate the efficacy and safety of BR1733 monotherapy (Cohorts 1-5) in five separate cohorts.

Study Timeline

• Study First Submitted: 2023-02-16
• Study First Submitted QC: 2023-02-27
• Study First Posted: 2023-03-01
• Study Start: 2023-04-19
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-05
• Last Update Posted: 2024-08-07
• Primary Completion: 2025-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 191

Inclusion Criteria

1. Sign informed consent voluntarily.
2. Subjects with PTCL, DLBCL or advance solid tumors diagnosed by histology or cytology，whose disease progressed after standard treatment or have no standard treatment.
3. ECOG≤2.
4. Expected survival period ≥ 3 months.
5. Adequate organ function reserve at baseline.

Exclusion Criteria

1. Subjects with symptomatic central nervous system (CNS) metastases or carcinomatous meningitis;
2. Subjects with a history of other primary malignancies within 5 years (except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumor), subjects with other primary tumors who had no evidence of disease for 5 years or more and did not require treatment could participate in the study;
3. Subjects with any severe uncontrolled disease such as liver disease such as cirrhosis, decompensated liver disease, kidney failure needs for hemodialysis or peritoneal dialysis, etc.
4. Subjects with HIV disease or a positive HIV test; or active hepatitis.
5. Subjects with organ transplantation (apart from keratoplasty) or allogeneic hematopoietic stem cell transplantation.
6. Subjects with impaired or clinically significant cardiac cerebrovascular disease.
7. Subjects known to be allergic to experimental drugs or similar compounds.
8. Subjects known with psychotropic substance abuse, alcohol or drug abuse, or mental disorders.
9. Any previous treatment with other EED inhibitors (e.g., MAK683, FTX-6058, etc.).
10. Females who are pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BR1733	BR1733	25-1200 mg QD or BID

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity (DLT, Phase Ⅰ only)	28 day cycle of therapy	To assess adverse events as dose limiting toxicities as defined by the protocol.
Objective Response Rate (ORR, Phase Ⅱa)	24 months	The proportion of patients with a best response of at least partial remission (including partial remission and complete remission) using disease appropriate standardized response criteria.

Secondary Outcome Measures

Name	Time	Method
Area under curve (AUC) of BR1733 monotherapy	28 day cycle of therapy	Pharmacokinetics profile of BR1733 (plasma): Area under curve (AUC)
Area under curve, steady state (AUCss) of BR1733 monotherapy	28 day cycle of therapy	Pharmacokinetics profile of continuous medication of BR1733 (plasma): Area under curve, steady state (AUCss)
Halflife (T1/2) of BR1733 monotherapy	28 day cycle of therapy	Pharmacokinetics profile of BR1733 (plasma): Halflife (T1/2)
Maximum plasma concentration, steady state (Cmax,ss) of BR1733 monotherapy	28 day cycle of therapy	Pharmacokinetics profile of continuous medication of BR1733 (plasma): Maximum plasma concentration, steady state (Cmax,ss)
Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability	Up to 2 years	Adverse events assessed according to NCI-CTCAE v5.0 criteria.
Maximum plasma concentration (Cmax) of BR1733 monotherapy	28 day cycle of therapy	Pharmacokinetics profile of BR1733 (plasma): Maximum plasma concentration (Cmax)
Progression-free survival (PFS)	Up to 2 years	PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression or death which occurs first
Clearance/ bioavailability (CL/F) of BR1733 monotherapy	28 day cycle of therapy	Pharmacokinetics profile of BR1733 (plasma): Clearance/bioavailability (CL/F)
Duration of Response (DoR)	Up to 2 years	DoR is defined as the duration (days) from initial response to disease relapse, progression, or death due to any course.
Overall Survival (OS)	Up to 2 years	OS is defined as the interval of time between the date of first treatment until death, loss to follow up or termination of the study by the sponsor

Trial Locations

Locations (1)

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; 🇨🇳 Tianjin, China