Phase I/IIa Study of BR790 in Combination With Tislelizumab in Adult Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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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
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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 .

Official Title
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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

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: BR790+Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign informed consent voluntarily. Age ≥18 and ≤75 years old. Subjects with advanced solid tumors diagnosed by histology or cytology，whose desease progressed after standard treatment or have no standard treatment. Had at least one measurable lesion. ECOG≤1. Expected survival period ≥ 3 months. Exclusion Criteria: Any previous treatment with SHP-2 inhibitor. Symptomatic brain metastases. Subjects with thoracic/ascites fluid that need drainage or intervention. 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. With uncontrolled severe disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BR790+Tislelizumab dose escalation<br>Dose escalation part | Drug: BR790+Tislelizumab<br>* BR790 will be administered orally, variable dose. Tislelizumab will be administered as an intravenous infusion,fixed dose.<br>|
| Experimental: BR790+Tislelizumab dose expansion<br>Dose expansion part | Drug: BR790+Tislelizumab<br>* BR790 will be administered orally, variable dose. Tislelizumab will be administered as an intravenous infusion,fixed dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) | Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle. (Dose escalation phase) | 24 months | 
| maximum tolerated dose (MTD) | Measurements of MTD (i.e. the highest dose of BR790 associated with the occurrence of Dose Limiting Toxicities (DLTs) in <33% of patients) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC) | Area under the plasma concentration time curve of BR790 | 24 months | 
| Plasma concentration (Cmax) | Highest observed plasma concentration of BR790 | 24 months | 
| t1/2 | Half life of BR790 | 24 months | 
| Duration of response ( DCR ) | DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD). (Dose escalation phase) | 24 months | 
| Duration of response ( DOR ) | DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first. (Dose escalation phase) | 24 months | 
| 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. (Dose escalation phase) | 24 months | 
| 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(Dose escalation phase) | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BR790,SHP2, checkpoint inhibitor, PD-1, NSCLC, CRC, HNSCC