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

A Multicenter, Open-Label Phase I/IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics/ Pharmacodynamics and Efficacy of BR1733 Monotherapy in Subjects With Advanced Cancers

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Follicular Lymphoma; Diffuse Large B Cell Lymphoma; Advanced Cancer; Peripheral T Cell Lymphoma
• Intervention / Treatment: Drug: BR1733

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 Type: Interventional
• Enrollment (Anticipated): 191
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BR1733; 25-1200 mg QD or BID	Drug: BR1733; Subjects will receive oral administration of BR1733.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity (DLT, Phase Ⅰ only)	To assess adverse events as dose limiting toxicities as defined by the protocol.	28 day cycle of therapy
Objective Response Rate (ORR, Phase Ⅱa)	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.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Halflife (T1/2) of BR1733 monotherapy	Pharmacokinetics profile of BR1733 (plasma): Halflife (T1/2)	28 day cycle of therapy
Area under curve (AUC) of BR1733 monotherapy	Pharmacokinetics profile of BR1733 (plasma): Area under curve (AUC)	28 day cycle of therapy
Maximum plasma concentration (Cmax) of BR1733 monotherapy	Pharmacokinetics profile of BR1733 (plasma): Maximum plasma concentration (Cmax)	28 day cycle of therapy
Area under curve, steady state (AUCss) of BR1733 monotherapy	Pharmacokinetics profile of continuous medication of BR1733 (plasma): Area under curve, steady state (AUCss)	28 day cycle of therapy
Maximum plasma concentration, steady state (Cmax,ss) of BR1733 monotherapy	Pharmacokinetics profile of continuous medication of BR1733 (plasma): Maximum plasma concentration, steady state (Cmax,ss)	28 day cycle of therapy
Clearance/ bioavailability (CL/F) of BR1733 monotherapy	Pharmacokinetics profile of BR1733 (plasma): Clearance/bioavailability (CL/F)	28 day cycle of therapy
Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability	Adverse events assessed according to NCI-CTCAE v5.0 criteria.	Up to 2 years
Duration of Response (DoR)	DoR is defined as the duration (days) from initial response to disease relapse, progression, or death due to any course.	Up to 2 years
Overall Survival (OS)	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	Up to 2 years
Progression-free survival (PFS)	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	Up to 2 years

Collaborators and Investigators

• Sponsor: Shanghai Blueray Biopharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): May 1, 2026

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, T-Cell; Neoplasms; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell, Peripheral
• Other Study ID Numbers: BR1733-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No