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

NSCLC Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06032936
• Other study ID #: LB1002-102
• Status: Recruiting
• Phase: Phase 1
• Start date: July 27, 2023
• Est. completion date: July 2026

Study information

• Verified date: September 2023
• Source: LianBio LLC
• Contact: Lei Mu, Master
• Phone: +86-021-23081188
• Email: lei.mu[@]lianbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: July 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Changchun	Jilin
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	Sun Yat-sen University Cancer Center	Guanzhou	Guangdong
China	Shandong Cancer Hospital	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
LianBio LLC

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Serious adverse events (SAEs)	Incidence and severity of Serious adverse events (SAEs)	Administration to approximately 28 days after the last study administration
Primary	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	Phase Ia: QT Interval	Evaluated by comparing the changes using electrocardiogram in the post-dose to the pre-dose.	Approximately 6 months
Secondary	Maximum plasma concentration (Cmax)	To characterize the pharmacokinetic parameter Maximum plasma concentration (Cmax) of BBP-398 and/or Osimertinib and its metabolites	Approximately 6 months
Secondary	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	Approximately 6 months
Secondary	Time to Reach Maximum Plasma Concentration (Tmax)	To characterize the pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of BBP-398 and/or Osimertinib and its metabolites.	Approximately 6 months
Secondary	Apparent total plasma clearance (CL/F)	To characterize the pharmacokinetic parameter Apparent total plasma clearance (CL/F) of BBP-398 and/or Osimertinib and its metabolites.	Approximately 6 months
Secondary	Terminal elimination half-life (t1/2)	To characterize the pharmacokinetic parameter Terminal elimination half-life (t1/2) of BBP-398 and/or Osimertinib and its metabolites.	Approximately 6 months
Secondary	Accumulation ratio (Racc)	To characterize the pharmacokinetic parameter Accumulation ratio (Racc) of BBP-398 and/or Osimertinib and its metabolites.	Approximately 6 months
Secondary	Phase Ib: DOR	DOR assessed by the investigator according to RECIST v1.1. DoR is defined as time interval from the first evaluation as CR or PR to the first evaluation as PD or death of any cause assessed by the investigator (percent of patients with =6 months, =9 months, and =12 months DoR will be reported).	Every 8 weeks from first evaluation as CR or PR to the first evaluation as PD or death of any cause, whichever came first, assessed approximately 24 months.
Secondary	Phase Ib: PFS	PFS assessed by the investigator according to RECIST v1.1. PFS is defined from the first date of treatment to the date of progression determined by the investigator or death due to any cause (only for dose expansion).	Every 8 weeks from first evaluation as CR or PR to the first evaluation as PD or death of any cause, whichever came first, assessed approximately 24 months.
Secondary	Phase Ib: OS	including 1-year and 2-years survival rate. OS is defined from the first date of treatment until date of death (only for dose expansion).	From the first date of treatment until date of death, assessed approximately 48 months.