Clinical trial

An Open-label, Non-randomized, Multi-cohort, Multi-center Phase Ia/Ib Study Evaluating the Efficacy and Safety of BBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations

Name

LB1002-102

Description

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.

Trial arms

Trial start

2023-07-27

Estimated PCD

2025-12-01

Trial end

2026-07-01

Status

Recruiting

Phase

Early phase I

Treatment

BBP-398

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.

Arms:

BBP-398 + Osimertinib

Other names:

IACS-15509

osimertinib

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.

Arms:

BBP-398 + Osimertinib

Size

Primary endpoint

Treatment-emergent adverse events (TEAEs)

From the first study administration to approximately 28 days after the last study administration

Serious adverse events (SAEs)

Administration to approximately 28 days after the last study administration

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

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.

Eligibility criteria

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.

Protocol

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Updated at

2023-09-13

1 organization

2 products

1 indication

Product

Indication

Organization

Product