This is an open label, dose escalation and expansion, two-part Phase I study for SHP-2 inhibitor BBP-398 to evaluate the safety, tolerability, pharmacokinetics, determine MTD and/or RP2D, and preliminary anti- cancer activity in Chinese subjects with advanced solid tumors and in Chinese subjects with advanced or metastatic EGFR-mutant NSCLC.
The Part A of this phase I trial is an abbreviated dose escalation study of BBP-398 following the USA mono dose escalation study (Study NAV- 1001, clinicaltrials.gov ID NCT04528836). The purpose of this part is to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer activity in Chinese subjects with advanced solid tumors. The Part B of this study is to explore the safety, tolerability and efficacy of BBP-398 in Chinese subjects with advanced or metastatic EGFR- mutant NSCLC at MTD and/or RP2D. This Phase I study will provide supportive data to enable Chinese patients to join the combo dose escalation and expansion studies and/or other clinical trials of BBP-398.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
BBP-398 (formerly known as IACS-15509) is a potent, selective, orally active allosteric inhibitor of SHP2, a tyrosine phosphatase that plays a key role in the RTK -MAPK signal transduction pathway. Key components of the MAPK pathway include the small GTPase RAS, the serine/threonine-protein kinase RAF, mitogen-activated protein kinase (MEK) and ERK. In cells, SHP2 binds to phosphorylated tyrosine residues in the intracellular domain of RTKs such as the EGFR, leading to activation of the downstream MAPK signaling pathway.
Sun Yat-sen University Cancer Center
Guanzhou, Guangdong, China
West China Hospital Sichuan University
Chengdu, Sichuan, China
Determination of Maximum Tolerated Dose (MTD) of BBP-398
The MTD will be based on DLT
Time frame: Completion of 1 Cycle (28 days)
Determination of anti-tumor activity of BBP-398
Anti-tumor activity will be defined by objective response rate (ORR, complete response + partial response rate) and duration of response (DOR) according to RECIST v1.1
Time frame: Completion of 1 Cycle (28 days)
Part A:Maximum plasma concentration (Cmax) of BBP-398
Maximum plasma concentration of BBP-398 after single and multiple dose administration of BBP-398
Time frame: Approximately 6 months
Part A:Time to reach Cmax (Tmax) of BBP-398
The amount of time to reach Cmax after single and multiple dose administration of BBP-398
Time frame: Approximately 6 months
Part A: Terminal half-life (t1/2) of BBP-398
Terminal half-life (t1/2) after single and multiple dose administration of BBP-398
Time frame: Approximately 6months
Part A: Area under the plasma concentration-time curve (AUC) of BBP-398
Area under the plasma concentration versus time curve after single and multiple dose administration of BBP-398
Time frame: Approximately 6 months
Part A: Concentration of BBP-398 in urine
To evaluate BBP-398 excretion via urine after single and multiple dose administration of BBP-398.
Time frame: Approximately 6 months
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Part B: Concentration of BBP-398 in plasma
To evaluate BBP-398 plasma concentration after multiple dose administration of BBP-398.
Time frame: Approximately 6 months