NSCLCPhase 1NCT06032936
BBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations
A Phase 1 study testing BBP-398 and osimertinib in people with NSCLC, run by LianBio LLC at 5 sites in China.
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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- NSCLC
- What is being tested?
- BBP-398 and osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 5 sitesChina
- Study dates
- 27 Jul 2023to 29 Mar 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142
Jilin Cancer Hospital
Changchun, Jilin, 130012
West China Hospital Sichuan University
Chengdu, Sichuan, 610041
Sun Yat-sen University Cancer Center
Guanzhou, Guangdong, 510060
Shandong Cancer Hospital
Jinan, Shandong, 250117
About this study
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
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
- Being tested
- BBP-398, osimertinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BBP-398Drug
Also called IACS-15509
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.
osimertinibDrug
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 group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: BBP-398; Drug: osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-emergent adverse events (TEAEs)
Incidence and severity of treatment-emergent adverse events (TEAEs).
Measured: 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)
Measured: 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.
Measured: 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
Evaluated by comparing the changes using electrocardiogram in the post-dose to the pre-dose.
Measured: Approximately 6 months
Maximum plasma concentration (Cmax)
To characterize the pharmacokinetic parameter Maximum plasma concentration (Cmax) of BBP-398 and/or Osimertinib and its metabolites
Measured: Approximately 6 months
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
Measured: Approximately 6 months
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.
Measured: Approximately 6 months
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.
Measured: Approximately 6 months
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.
Measured: Approximately 6 months
Accumulation ratio (Racc)
To characterize the pharmacokinetic parameter Accumulation ratio (Racc) of BBP-398 and/or Osimertinib and its metabolites.
Measured: Approximately 6 months
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).
Measured: 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.
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).
Measured: 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.
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).
Measured: From the first date of treatment until date of death, assessed approximately 48 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2023
- Study start27 Jul 2023
- Primary completion29 Mar 2024
- Study completion29 Mar 2024
Why it stopped: Business reason
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- LianBio LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Li Zhang, Master, Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06032936
- Sponsor's protocol ID
- LB1002-102
- Status last verified
- Jun 2024
- First submitted
- 31 Jul 2023
- Last updated
- 25 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06032936
- Acronym / sponsor ID
- LB1002-102
- Conditions
- NSCLC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reason
- Enrolment
- 4 participants (actual)
- Lead sponsor
- LianBio LLCIndustry (pharma, biotech, devices)
- Study start
- 27 Jul 2023 (actual)
- Primary completion
- 29 Mar 2024 (actual)
- Study completion
- 29 Mar 2024 (actual)
- First posted
- 13 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BBP-398 + Osimertinib | Experimental | Drug: BBP-398, Drug: osimertinibPhase 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 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BBP-398Also: IACS-15509BBP-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. | Drug | BBP-398 + Osimertinib |
| osimertinibOsimertinib 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. | Drug | BBP-398 + Osimertinib |
Primary outcome
Treatment-emergent adverse events (TEAEs)
Time frame: From the first study administration to approximately 28 days after the last study administration
Incidence and severity of treatment-emergent adverse events (TEAEs).
Serious adverse events (SAEs)
Time frame: Administration to approximately 28 days after the last study administration
Incidence and severity of Serious adverse events (SAEs)
Phase Ib: ORR assessed by the investigator according to RECIST v1.1
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.
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.
10 secondary outcomes
Phase Ia: QT Interval
Time frame: Approximately 6 months
Maximum plasma concentration (Cmax)
Time frame: Approximately 6 months
Area under the plasma concentration versus time curve (AUC)
Time frame: Approximately 6 months
Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: Approximately 6 months
Apparent total plasma clearance (CL/F)
Time frame: Approximately 6 months
Terminal elimination half-life (t1/2)
Time frame: Approximately 6 months
Accumulation ratio (Racc)
Time frame: Approximately 6 months
Phase Ib: DOR
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.
Phase Ib: PFS
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.
Phase Ib: OS
Time frame: From the first date of treatment until date of death, assessed approximately 48 months.
Results and safety
The study was stopped early (reason given: Business reason). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Li Zhang, Master principal investigator
Sun Yat-sen University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BBP-398 and osimertinib in people with NSCLC, run by LianBio LLC at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business reason). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-emergent adverse events (TEAEs) (time frame: From the first study administration to approximately 28 days after the last study administration). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.