Back to resultsBBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations
Primary Purpose
NSCLC
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
BBP-398
osimertinib
Sponsored by
About this trial
This is an interventional treatment trial for NSCLC
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.
Sites / Locations
- Beijing Cancer Hospital
- Sun Yat-sen University Cancer CenterRecruiting
- Jilin Cancer Hospital
- Shandong Cancer Hospital
- West China Hospital Sichuan UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BBP-398 + Osimertinib
Arm Description
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
Outcomes
Primary Outcome Measures
Treatment-emergent adverse events (TEAEs)
Incidence and severity of treatment-emergent adverse events (TEAEs).
Serious adverse events (SAEs)
Incidence and severity of Serious adverse events (SAEs)
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.
Secondary Outcome Measures
Phase Ia: QT Interval
Evaluated by comparing the changes using electrocardiogram in the post-dose to the pre-dose.
Maximum plasma concentration (Cmax)
To characterize the pharmacokinetic parameter Maximum plasma concentration (Cmax) of BBP-398 and/or Osimertinib and its metabolites
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 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.
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.
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.
Accumulation ratio (Racc)
To characterize the pharmacokinetic parameter Accumulation ratio (Racc) of BBP-398 and/or Osimertinib and its metabolites.
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).
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).
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT06032936
Brief Title
BBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 27, 2023 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
July 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LianBio LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NSCLC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
BBP-398 + Osimertinib
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
BBP-398
Other Intervention Name(s)
IACS-15509
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
osimertinib
Intervention Description
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.
Primary Outcome Measure Information:
Title
Treatment-emergent adverse events (TEAEs)
Description
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
Title
Serious adverse events (SAEs)
Description
Incidence and severity of Serious adverse events (SAEs)
Time Frame
Administration to approximately 28 days after the last study administration
Title
Phase Ib: ORR assessed by the investigator according to RECIST v1.1
Description
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 Outcome Measure Information:
Title
Phase Ia: QT Interval
Description
Evaluated by comparing the changes using electrocardiogram in the post-dose to the pre-dose.
Time Frame
Approximately 6 months
Title
Maximum plasma concentration (Cmax)
Description
To characterize the pharmacokinetic parameter Maximum plasma concentration (Cmax) of BBP-398 and/or Osimertinib and its metabolites
Time Frame
Approximately 6 months
Title
Area under the plasma concentration versus time curve (AUC)
Description
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
Title
Time to Reach Maximum Plasma Concentration (Tmax)
Description
To characterize the pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) of BBP-398 and/or Osimertinib and its metabolites.
Time Frame
Approximately 6 months
Title
Apparent total plasma clearance (CL/F)
Description
To characterize the pharmacokinetic parameter Apparent total plasma clearance (CL/F) of BBP-398 and/or Osimertinib and its metabolites.
Time Frame
Approximately 6 months
Title
Terminal elimination half-life (t1/2)
Description
To characterize the pharmacokinetic parameter Terminal elimination half-life (t1/2) of BBP-398 and/or Osimertinib and its metabolites.
Time Frame
Approximately 6 months
Title
Accumulation ratio (Racc)
Description
To characterize the pharmacokinetic parameter Accumulation ratio (Racc) of BBP-398 and/or Osimertinib and its metabolites.
Time Frame
Approximately 6 months
Title
Phase Ib: DOR
Description
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).
Time Frame
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.
Title
Phase Ib: PFS
Description
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).
Time Frame
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.
Title
Phase Ib: OS
Description
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).
Time Frame
From the first date of treatment until date of death, assessed approximately 48 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Mu, Master
Phone
+86-021-23081188
Email
lei.mu@lianbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Li Zhang, Master
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Zhao
Phone
+8613521469355
Email
ohjerry@163.com
Facility Name
Sun Yat-sen University Cancer Center
City
Guanzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li Zhang, Master
Phone
+86-020-87343458
Email
zhangli@sysucc.org.cn
Facility Name
Jilin Cancer Hospital
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130012
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ying Cheng
Phone
+8613943012851
Email
jl.cheng@163.com
Facility Name
Shandong Cancer Hospital
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250117
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yintao Li
Phone
+8615169045166
Email
liyintaosky@gmail.com
Facility Name
West China Hospital Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongsheng Wang, Doctor
Phone
+8618980602258
Email
wangy756@163.com
12. IPD Sharing Statement
Learn more about this trial
BBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations
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