Ignite Creation Date:
2025-12-25 @ 1:32 AM
Ignite Modification Date:
2025-12-31 @ 7:15 PM
Study NCT ID:
NCT06930794
Status:
RECRUITING
Last Update Posted:
2025-12-05
First Post:
2025-02-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of Vebreltinib and Platinum-Containing Double Agents in Subjects With MET Amplification.
Sponsor:
Beijing Pearl Biotechnology Limited Liability Company
Organization:
Study Overview
Official Title:
An Open-label, Randomized, Controlled, Multicenter Phase IIIb Clinical Study to Evaluate the Efficacy and Safety of Vebreltinib Enteric Capsule Combined With Platinum-based Doublet Chemotherapy Compared With Platinum-based Doublet Chemotherapy in Subjects With Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Not Received Previous Systemic Treatment and Carry MET Amplification.
Status:
RECRUITING
Status Verified Date:
2025-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
KUNPENG-3
Brief Summary:
This study is an open-label, randomized, controlled, multicenter Phase IIIb clinical study, aiming to evaluate the efficacy, safety, and tolerability of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy compared with platinum-based doublet chemotherapy in treating subjects with locally advanced or metastatic non-squamous NSCLC who have not received previous systemic treatment and carry MET amplification.
The target population of this study is subjects with histologically confirmed locally advanced or metastatic non-squamous NSCLC who have not received previous systemic anti-tumor treatment and carry MET amplification.
This study adopts an enrichment design. The enriched population is those with MET GCN ≥ 6, and the overall population is those with MET GCN ≥ 4.
This study consists of two parts: the lead-in period (Part 1) and the randomized controlled period (Part 2). Both the lead-in period (Part 1) and the randomized controlled period (Part 2) will include a screening period (from Day -28 to Day -1), a treatment period (until the termination of treatment), and a follow-up period (including safety follow-up and survival follow-up).
The target population of this study is subjects with histologically confirmed locally advanced or metastatic non-squamous NSCLC who have not received previous systemic anti-tumor treatment and carry MET amplification.
This study adopts an enrichment design. The enriched population is those with MET GCN ≥ 6, and the overall population is those with MET GCN ≥ 4.
This study consists of two parts: the lead-in period (Part 1) and the randomized controlled period (Part 2). Both the lead-in period (Part 1) and the randomized controlled period (Part 2) will include a screening period (from Day -28 to Day -1), a treatment period (until the termination of treatment), and a follow-up period (including safety follow-up and survival follow-up).
Detailed Description:
Part 1 (Lead-in Period):
The lead-in period is set before the randomized controlled period, aiming to evaluate the safety, tolerability, and preliminary efficacy of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy, and to determine the recommended dose of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy. Initially, it is planned to set up 2 dose groups in the lead-in period. After the screening period, eligible subjects will be assigned to the 2 dose cohorts in chronological order, and the subjects will receive oral treatment of Vebreltinib Enteric Capsule at different doses combined with intravenous chemotherapy of standard-dose platinum-based doublet according to the cohort assignment.
Vebreltinib Enteric Capsule: Each cycle is 3 weeks (21 days), administered orally twice a day (BID), and the dose level depends on the cohort assignment.
Platinum-based doublet chemotherapy: Each cycle is 3 weeks (21 days), and it is administered once on Day 1 (D1) of each cycle. Pemetrexed 500 mg/m² + platinum (carboplatin AUC5 or cisplatin 75 mg/m²) is given by intravenous infusion for 4 to 6 cycles as the initial treatment, and then it is switched to pemetrexed (500 mg/m²) by intravenous infusion as the maintenance treatment.
In this part, the "3+3" dose escalation design will be adopted to determine the maximum tolerated dose (MTD) and/or the recommended dose of the combination of Vebreltinib Enteric Capsule and platinum-based doublet treatment in subjects with locally advanced or metastatic non-squamous NSCLC.
Part 2 (Randomized Controlled Period):
After completing the lead-in period study in Part 1, once the investigator and the sponsor have determined the recommended dose of the combination of Vebreltinib Enteric Capsule, the randomized controlled study in Part 2 will be carried out to evaluate the efficacy of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy compared with platinum-based doublet chemotherapy in subjects with locally advanced or metastatic non-squamous NSCLC carrying MET amplification.
After the screening period, eligible subjects will be stratified according to the stratification factors (baseline brain metastasis status \[yes vs no\], MET gene copy number \[GCN\] \[≥4 and \<6 vs ≥6 and \<10 vs ≥10\]) and randomly assigned to the experimental group or the control group at a 1:1 allocation ratio using the stratified block randomization method. The experimental group will receive the treatment regimen of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy, and the control group will receive the platinum-based doublet chemotherapy regimen.
Subjects randomly assigned to the control group will have the opportunity to choose to receive single-agent treatment with Vebreltinib Enteric Capsule (200 mg BID) after the disease progression is evaluated by the investigator and confirmed by the blinded independent central review (BICR). Receiving single-agent treatment with Vebreltinib Enteric Capsule after progression is not mandatory and is determined by the investigator at his/her own discretion (subject to the approval of the sponsor).
Number of subjects: It is expected to enroll 6-18 subjects in the dose escalation stage of the lead-in period, and about 10-20 subjects in the cohort expansion stage, with a total of about 16-38 subjects to be enrolled (the final number will depend on the number of dose levels). The planned sample size of the enriched population with GCN≥6 in the randomized controlled period is 182 cases. Considering that the proportion of the enriched population with GCN≥6 in the general population is approximately 75%, the estimated sample size of the total population is 242.
Independent Data Monitoring Committee (IDMC): During the interim analysis, the independent statistical team of the IDMC will conduct the interim analysis, which will be evaluated by the IDMC experts, and the IDMC will give its recommendations.
The lead-in period is set before the randomized controlled period, aiming to evaluate the safety, tolerability, and preliminary efficacy of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy, and to determine the recommended dose of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy. Initially, it is planned to set up 2 dose groups in the lead-in period. After the screening period, eligible subjects will be assigned to the 2 dose cohorts in chronological order, and the subjects will receive oral treatment of Vebreltinib Enteric Capsule at different doses combined with intravenous chemotherapy of standard-dose platinum-based doublet according to the cohort assignment.
Vebreltinib Enteric Capsule: Each cycle is 3 weeks (21 days), administered orally twice a day (BID), and the dose level depends on the cohort assignment.
Platinum-based doublet chemotherapy: Each cycle is 3 weeks (21 days), and it is administered once on Day 1 (D1) of each cycle. Pemetrexed 500 mg/m² + platinum (carboplatin AUC5 or cisplatin 75 mg/m²) is given by intravenous infusion for 4 to 6 cycles as the initial treatment, and then it is switched to pemetrexed (500 mg/m²) by intravenous infusion as the maintenance treatment.
In this part, the "3+3" dose escalation design will be adopted to determine the maximum tolerated dose (MTD) and/or the recommended dose of the combination of Vebreltinib Enteric Capsule and platinum-based doublet treatment in subjects with locally advanced or metastatic non-squamous NSCLC.
Part 2 (Randomized Controlled Period):
After completing the lead-in period study in Part 1, once the investigator and the sponsor have determined the recommended dose of the combination of Vebreltinib Enteric Capsule, the randomized controlled study in Part 2 will be carried out to evaluate the efficacy of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy compared with platinum-based doublet chemotherapy in subjects with locally advanced or metastatic non-squamous NSCLC carrying MET amplification.
After the screening period, eligible subjects will be stratified according to the stratification factors (baseline brain metastasis status \[yes vs no\], MET gene copy number \[GCN\] \[≥4 and \<6 vs ≥6 and \<10 vs ≥10\]) and randomly assigned to the experimental group or the control group at a 1:1 allocation ratio using the stratified block randomization method. The experimental group will receive the treatment regimen of Vebreltinib Enteric Capsule combined with platinum-based doublet chemotherapy, and the control group will receive the platinum-based doublet chemotherapy regimen.
Subjects randomly assigned to the control group will have the opportunity to choose to receive single-agent treatment with Vebreltinib Enteric Capsule (200 mg BID) after the disease progression is evaluated by the investigator and confirmed by the blinded independent central review (BICR). Receiving single-agent treatment with Vebreltinib Enteric Capsule after progression is not mandatory and is determined by the investigator at his/her own discretion (subject to the approval of the sponsor).
Number of subjects: It is expected to enroll 6-18 subjects in the dose escalation stage of the lead-in period, and about 10-20 subjects in the cohort expansion stage, with a total of about 16-38 subjects to be enrolled (the final number will depend on the number of dose levels). The planned sample size of the enriched population with GCN≥6 in the randomized controlled period is 182 cases. Considering that the proportion of the enriched population with GCN≥6 in the general population is approximately 75%, the estimated sample size of the total population is 242.
Independent Data Monitoring Committee (IDMC): During the interim analysis, the independent statistical team of the IDMC will conduct the interim analysis, which will be evaluated by the IDMC experts, and the IDMC will give its recommendations.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: