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

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.

Inclusion criteria

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

Exclusion criteria

• Subjects with symptomatic central nervous system (CNS) metastases or carcinomatous meningitis;
• 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;
• 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.
• Subjects with HIV disease or a positive HIV test; or active hepatitis.
• Subjects with organ transplantation (apart from keratoplasty) or allogeneic hematopoietic stem cell transplantation.
• Subjects with impaired or clinically significant cardiac cerebrovascular disease.
• Subjects known to be allergic to experimental drugs or similar compounds.
• Subjects known with psychotropic substance abuse, alcohol or drug abuse, or mental disorders.
• Any previous treatment with other EED inhibitors (e.g., MAK683, FTX-6058, etc.).
• Females who are pregnant or breastfeeding.