BBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations

Phase 1TerminatedNCT06032936

LianBio LLC4 enrolled

Overview

This is an open-label, non-randomized, multi-cohort, multi-center Phase Ia/Ib study for BBP-398 in combination with Osimertinib to evaluate the safety, tolerability, pharmacokinetics, determine MTD and/or RP2D, and anti-cancer activity in locally advanced or metastatic NSCLC patients with EGFR mutations and with previously 3rd generation EGFR-TKIs treated or EGFR-TKI-naive.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

NSCLC

Interventions

BBP-398DRUG

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.

osimertinibDRUG

Osimertinib is a mutant-selective, third-generation EGFR inhibitor that targets both EGFR-activating mutations (e.g., exon 19 deletion and L858R) and EGFR-dependent on-target resistance mutation toward the 1st generation EGFR inhibitor (i.e., T790M). It is currently a first-line therapy for EGFR-mutant (EGFRmut) NSCLC, with average progression-free survival of approximately 19 months in previously untreated subjects.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients must have the ability to understand and the willingness to sign a written informed consent document. * Patients must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures. * Age ≥18, male or female. * Patients are not suitable for surgical resection and must have histologically or cytologically confirmed advanced or metastatic NSCLC with documented EGFR sensitivity mutation (at any time since the initial diagnosis of NSCLC) to confirm susceptibility to EGFR-TKI therapy. * Patients must have measurable disease by RECIST v1.1. * ECOG performance status ≤2. * Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening. * Patients must have adequate organ function. Exclusion Criteria: * Patients with a known additional malignancy that is progressing or requires active treatment. * Patients who have previously received a SHP-2 inhibitor. * Patients who are hypersensitivity to BBP-398/ Osimertinib or active or inactive excipients. * Treatment with any of the following anti-cancer therapies prior to the first dose within the stated timeframes. * Pregnant or breastfeeding female patients. * Patients with untreated symptomatic brain metastases and/or meningeal metastases.

Locations (5)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Sun Yat-sen University Cancer Center

Guanzhou, Guangdong, China

Jilin Cancer Hospital

Changchun, Jilin, China

Shandong Cancer Hospital

Jinan, Shandong, China

Outcomes

Primary Outcomes

Treatment-emergent adverse events (TEAEs)

Incidence and severity of treatment-emergent adverse events (TEAEs).

Time frame: From the first study administration to approximately 28 days after the last study administration

Serious adverse events (SAEs)

Incidence and severity of Serious adverse events (SAEs)

Time frame: Administration to approximately 28 days after the last study administration

Phase Ib: ORR assessed by the investigator according to RECIST v1.1

ORR is defined as number of patients with confirmed responses of CR or PR, divided by the total number of treated patients with measurable disease at baseline assessed by the investigator.

Time frame: Every 8 weeks from first dose administration to the date of progression determined by the investigator or death due to any cause, whichever came first, assessed approximately 48 months.

Secondary Outcomes

Phase Ia: QT Interval

Evaluated by comparing the changes using electrocardiogram in the post-dose to the pre-dose.

Time frame: Approximately 6 months

Maximum plasma concentration (Cmax)

To characterize the pharmacokinetic parameter Maximum plasma concentration (Cmax) of BBP-398 and/or Osimertinib and its metabolites

Time frame: Approximately 6 months

Area under the plasma concentration versus time curve (AUC)

To characterize the pharmacokinetic parameter Area under the plasma concentration versus time curve (AUC) of BBP-398 and/or Osimertinib and its metabolites

Time frame: Approximately 6 months

Data from ClinicalTrials.gov

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