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

Sponsor
LianBio LLC
Study ID
NCT06032936
Phase
PHASE1
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 99 Years
Healthy Volunteers
Not accepted

Interventions

  • BBP-398 — DRUG
    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.
  • osimertinib — DRUG
    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.

Study Details

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.

Key Dates

Start date
Jul 27, 2023
Status verified
Jun 2024
Primary completion
Mar 29, 2024
Completion
Mar 29, 2024

Study Design

Enrollment
4 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: BBP-398 + Osimertinib
    Phase Ia (Dose Escalation): Dose level 1: (starting dose level) The one lower dose level than RP2D of BBP-398 monotherapy in Chinese patients (RP2D -1) with Osimertinib 80 mg Dose level 2: RP2D The same dose level to RP2D of BBP-398 monotherapy in Chinese patients with Osimertinib 80 mg Note: The dosing interval and regimen might be changed based on emerging data of Study NAV-1001, LB1002-101 and this study. The proposed new dosing regimen will be submitted in a memo to EC for approval before execution. Phase Ib (Efficacy Expansion): Osimertinib 80mg QD + BBP-398 RP2D QD

Primary Outcome Measure

Treatment-emergent adverse events (TEAEs) [ Time Frame: From the first study administration to approximately 28 days after the last study administration ]

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