Clinical trial NCT05749549: Phase I/IIa Study of BR1733 in Subjects With Advanced Cancers
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Cancer
Follicular Lymphoma
Peripheral T Cell Lymphoma
Diffuse Large B Cell Lymphoma
Lead sponsor: Shanghai Blueray Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-03-01
Enrollment: 191
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT, Phase Ⅰ only)
timeFrame: 28 day cycle of therapy
measure: Objective Response Rate (ORR, Phase Ⅱa)
timeFrame: 24 months
Secondary outcomes:
measure: Halflife (T1/2) of BR1733 monotherapy
timeFrame: 28 day cycle of therapy
measure: Area under curve (AUC) of BR1733 monotherapy
timeFrame: 28 day cycle of therapy
measure: Maximum plasma concentration (Cmax) of BR1733 monotherapy
timeFrame: 28 day cycle of therapy
measure: Area under curve, steady state (AUCss) of BR1733 monotherapy
timeFrame: 28 day cycle of therapy
measure: Maximum plasma concentration, steady state (Cmax,ss) of BR1733 monotherapy
timeFrame: 28 day cycle of therapy
measure: Clearance/ bioavailability (CL/F) of BR1733 monotherapy
timeFrame: 28 day cycle of therapy
measure: Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 2 years
measure: Duration of Response (DoR)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Study officials:
References: