Clinical trial NCT05715398: BR790 in Combination With Anlotinib in Adult Subjects With Advanced Non-Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: BR790
Anlotinib
NSCLC
PTPN11
SHP2
Lead sponsor: Shanghai Gopherwood Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-02-08
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose/Recommended Phase Ⅱ Dose(MTD/RP2D)
timeFrame: 2 years
measure: Objective Response Rate (ORR)
timeFrame: 2 years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 2 years
measure: Duration of overall response (DOR)
timeFrame: 2 years
measure: Disease Control Rate(DCR)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Adverse Events(AEs)
timeFrame: 2 years
measure: Area under the plasma concentration-time curve (AUC)
timeFrame: 2 years
measure: Plasma concentration (Cmax)
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Shanghai Chest Hospital
name: Baohui Han
role: PRINCIPAL_INVESTIGATOR
References: