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

Shanghai Blueray Biopharma Co., Ltd.191 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

191

Conditions

Advanced Cancer Follicular Lymphoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Dose Limiting Toxicity (DLT, Phase Ⅰ only)

To assess adverse events as dose limiting toxicities as defined by the protocol.

Time frame: 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.

Time frame: 24 months

Secondary Outcomes

Halflife (T1/2) of BR1733 monotherapy

Pharmacokinetics profile of BR1733 (plasma): Halflife (T1/2)

Time frame: 28 day cycle of therapy

Area under curve (AUC) of BR1733 monotherapy

Pharmacokinetics profile of BR1733 (plasma): Area under curve (AUC)

Time frame: 28 day cycle of therapy

Maximum plasma concentration (Cmax) of BR1733 monotherapy

Pharmacokinetics profile of BR1733 (plasma): Maximum plasma concentration (Cmax)

Time frame: 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)

Time frame: 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)

Time frame: 28 day cycle of therapy

Clearance/ bioavailability (CL/F) of BR1733 monotherapy

Pharmacokinetics profile of BR1733 (plasma): Clearance/bioavailability (CL/F)

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: Up to 2 years

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes