Clinical trial NCT05505877: Phase I/IIa Study of BR790 in Combination With Tislelizumab in Adult Subjects With Advanced Solid Tumors
Official title: A Multicenter, Open-Label Phase 1/IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics and Efficacy of BR790 Tablets in Combination With Tislelizumab Injection in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Keywords: BR790,SHP2, checkpoint inhibitor, PD-1, NSCLC, CRC, HNSCC
Lead sponsor: Shanghai Gopherwood Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-18
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is a Phase I/IIa, multi-center, open-label study of BR790 in combination with Tislelizumab with a dose escalation part followed by a dose expansion part in adult subjects with advanced solid tumors.

These 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: Phase 1 (Dose Escalation Phase of BR790 Tablets Combined with Tislelizumab Injection): According to the incidence of DLT in BR790 Tablets Combined with Tislelizumab Injection Monoclonal Antibody in the Treatment of Advanced Solid Tumors, MTD and the Phase 2 clinical trial dose (RP2D) combining PK , efficacy and safety data were determined.

Stage II (BR790 Tablets combined with tislelizumab injection dose expansion stage): Evaluate the objective response rate (ORR) of BR790 Tablets combined with tislelizumab injection according to Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 .

Eligibility criteria: Inclusion Criteria:

1. Sign informed consent voluntarily.
2. Age ≥18 and ≤75 years old.
3. Subjects with advanced solid tumors diagnosed by histology or cytology，whose desease progressed after standard treatment or have no standard treatment.
4. Had at least one measurable lesion.
5. ECOG≤1.
6. Expected survival period ≥ 3 months.

Exclusion Criteria:

1. Any previous treatment with SHP-2 inhibitor.
2. Symptomatic brain metastases.
3. Subjects with thoracic/ascites fluid that need drainage or intervention.
4. Subjects with not enough organ functional reserve at baseline, which met at least one of the following criteria： ANC\<1.5×10\^9/L PLT\<100×10\^9/L Hb\<90g/L TBIL\>1.5×ULN ALT, AST\>2.5×ULN (without liver metastases) or ALT, AST\>5×ULN (with liver metastases), Cr \>1.5×ULN.
5. With uncontrolled severe disease.

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: 24 months
measure: maximum tolerated dose (MTD)
timeFrame: 24 months
Secondary outcomes:
measure: Area under the plasma concentration-time curve (AUC)
timeFrame: 24 months
measure: Plasma concentration (Cmax)
timeFrame: 24 months
measure: t1/2
timeFrame: 24 months
measure: Duration of response ( DCR )
timeFrame: 24 months
measure: Duration of response ( DOR )
timeFrame: 24 months
measure: Progression-free survival (PFS)
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangzhou
Study officials:
affiliation: Sun Yat-sen University
name: li zhang
role: PRINCIPAL_INVESTIGATOR
References: