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

NCT06032936 | Terminated Phase 1

• 1 other identifier: LB1002-102
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (3)

• Treatment-emergent adverse events (TEAEs)

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

  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)

  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.

  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 (10)

• Phase Ia: QT Interval

  Approximately 6 months

• Maximum plasma concentration (Cmax)

  Approximately 6 months

• Area under the plasma concentration versus time curve (AUC)

  Approximately 6 months

• Time to Reach Maximum Plasma Concentration (Tmax)

  Approximately 6 months

• Apparent total plasma clearance (CL/F)

  Approximately 6 months

Study Arms (1)

BBP-398 + Osimertinib

EXPERIMENTAL

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

Drug: BBP-398; Drug: osimertinib

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.

Also known as: IACS-15509

BBP-398 + Osimertinib

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.

BBP-398 + Osimertinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• LianBio LLC: lead

Study Sites (5)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Sun Yat-sen University Cancer Center

Guanzhou, Guangdong, 510060, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

Location

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

Location

West China Hospital Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Interventions

osimertinib

Study Officials

• Li Zhang, Master

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: September 13, 2023
• Study Start: July 27, 2023
• Primary Completion: March 29, 2024
• Study Completion: March 29, 2024
• Last Updated: June 25, 2024

Record last verified: 2024-06

Locations

CN (5)