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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: BR790+Tislelizumab

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 .

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: xiao Chen; Phone Number: 010-84682600; Email: chenxiao@gfmbiotech.com

Study Locations

• China
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Gopherwood Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 10, 2022
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: August 15, 2022
• First Submitted That Met QC Criteria: August 16, 2022
• First Posted (Actual): August 18, 2022

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: BR790,SHP2, checkpoint inhibitor, PD-1, NSCLC, CRC, HNSCC
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BR790-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No