BR790 in Combination With Anlotinib in Adult Subjects With Advanced Non-Small Cell Lung Cancer

A Multicenter, Open Phase Ⅰ/Ⅱa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BR790 in Combination With Anlotinib in Subjects With Advanced Non-small Cell Lung Cancer

This is a Phase Ⅰ/Ⅱa, multi-center, open-label study, aiming to evaluate the safety, tolerability, pharmacokinetic (PK), and efficacy of BR790 in combination with anlotinib in adult participants with advanced NSCLC.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: BR790+anlotinib

Detailed Description

This study is a Phase Ⅰ/Ⅱa, multi-center, open-label study of BR790 in combination with anlotinib with a dose escalation part followed by a dose expansion part in adult subjects with advanced NSCLC. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Baohui Han, professor; Phone Number: +86 18930858216; Email: 18930858216@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 and ≤75 years old.
• Subjects with histologically or cytologically confirmed locally advanced or relapsed metastatic driver negative (EGFR, ALK, ROS, etc.) advanced NSCLC，whose disease progressed after at least 2 previous standard therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) .

Exclusion Criteria:

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has uncontrolled moderate to massive effusion.
• Central lung squamous carcinoma along with cavum, or non-small cell lung cancer along with hemoptysis (>50ml/day).
• Other kinds of malignancies within 5 years or for now.
• Has 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<100g/L; TBIL>1.5×ULN, ALT or AST>2.5×ULN (without liver metastases) , ALT or AST>5×ULN (with liver metastases);Cr >1.5×ULN, urine protein≥++，or confirmed 24h urine protein≥1.0g;INR >1.5×ULN, PT>1.5ULN or APTT >1.5×ULN.
• Previous use of other SHP2 inhibitors (such as TNO-155, JAB-3312, JAB-3068, RLY-1971, RMC-4630, etc.)
• Has used anlotinib before
• The first assessment of efficacy was PD, or occurred ≥grade 3 adverse reactions with antitumor angiogenesis small-molecule drugs (e.g. Apatinib, surufatinib, fruquintinib, etc.), or less than 6 months after the last antitumor vascular therapy.
• Has got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (5.0), alopecia and grade 2 peripheral neuropathy are not included.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BR790+anlotinib; BR790 will be administered orally, variable dose on Day 1 of each 21-day cycle, Anlotinib will be administered as PO fixed dose on Day1-14 of each 21-day cycle	Drug: BR790+anlotinib; BR790 will be administered orally, variable dose on Day 1 of each 21-day cycle， Anlotinib will be administered as PO fixed dose on Day1-14 of each 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose/Recommended Phase Ⅱ Dose(MTD/RP2D)	To evaluate the MTD/RP2D of BR790 in combination with anlotinib (Part 1)	2 years
Objective Response Rate (ORR)	To evaluate the objective response rate (ORR) of BR790 in combination with anlotinib. ORR is defined as the proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) as assessed by RECIST v1.1 (Part 2)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the time from randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first.	2 years
Duration of overall response (DOR)	DOR is defined as the time from the first documented CR or PR per RECIST v1.1 to disease recurrence or disease progression (PD) whichever occurs first.	2 years
Disease Control Rate(DCR)	DCR is defined as the proportion of subjects who achieve a Complete Response (CR) 、Partial Response (PR) or Stable Disease (SD) as assessed by RECIST v1.1	2 years
Overall Survival (OS)	OS is defined as the time from study treatment initiation to death from any cause or last day known to be alive.	2 years
Adverse Events(AEs)	Incidence, nature, and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values and vital signs for combination therapy	2 years
Area under the plasma concentration-time curve (AUC)	Area under the plasma concentration time curve of BR790/anlotinib	2 years
Plasma concentration (Cmax)	Highest observed plasma concentration of BR790/anlotinib	2 years

Collaborators and Investigators

• Sponsor: Shanghai Gopherwood Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2023
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): December 1, 2025

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: February 2, 2023
• First Posted (ACTUAL): February 8, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; SHP2; PTPN11; Anlotinib; BR790
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: BR790-103

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