Vebreltinib Plus PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFRm, MET+, Locally Advanced or Metastatic NSCLC Following EGFR-TKI Failure (KYLIN-3)

A Randomized, Controlled, Open Label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of Vebreltinib in Combination With PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFR Mutations, MET Amplification and/or Overexpression, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Following EGFR-TKI Treatment Failure

Efficacy and Safety of Vebreltinib in Combination With PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFR Mutations, MET Amplification and/or Overexpression, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Following EGFR-TKI Treatment Failure

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: PLB1004; Drug: Vebreltinib; Drug: Pemetrexed plus Carboplatin or Cisplatin

Detailed Description

A Randomized, Controlled, Open Label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of Vebreltinib in Combination With PLB1004 Versus Platinum-based Doublet Chemotherapy in Patients With EGFR Mutations, MET Amplification and/or Overexpression, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Following EGFR-TKI Treatment Failure

• Study Type: Interventional
• Enrollment (Estimated): 278
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Liang Lin; Phone Number: +86-10-84148931; Email: linliang@avistonebio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent document.
2. Aged at least 18 years old.
3. Histologically or cytologically confirmed locally advanced or metastatic NSCLC (stage IIIB~IV).
4. At least one measurable lesion as defined by RECIST V1.1.
5. ECOG performance status 0 to 1.

Exclusion Criteria:

1. There are mutations of ALK or ROS1.
2. Have symptomatic and neurologically unstable central nervous system (CNS) metastases or CNS disease that requires increased steroid doses for control.
3. Before randomization, patients did not recover from any toxicity and/ or complications of previous chemotherapy, surgery, radiotherapy and other anti-cancer treatments, that is, did not fall to grade 1 or lower (National Cancer Research Common Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0), except for hair loss and irrecoverable permanent radiation damage.
4. Major surgery or had significant traumatic injury within 4 weeks prior to the first dose of the investigational product.
5. Pregnant or nursing women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vebreltinib 150mg BID plus PLB1004 80mg QD; Subjects will receive Vebreltinib 150mg orally twice per day (BID) plus PLB1004 80mg orally once per day (QD),21day cycles until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.	Drug: PLB1004; Subjects will receive PLB1004 80mg orally once per day (QD).; Other Names: Andamertinib; Drug: Vebreltinib; Subjects will receive Vebreltinib Enteric-coated Capsule orally twice per day (BID).; Other Names: Bozitinib; PLB1001
Active Comparator: Pemetrexed plus cisplatin/carboplatin; Subjects randomized to the control group will receive pemetrexed 500 mg/m² + platinum-based chemotherapy (carboplatin AUC 5 or cisplatin 75 mg/m²) via intravenous infusion for 4-6 cycles (determined by the investigator) as initial therapy, followed by pemetrexed maintenance therapy (500 mg/m²) until disease progression, intolerable toxicity, initiation of new antitumor therapy, death, loss to follow-up, or other treatment-terminating conditions (whichever occurred first)	Drug: Pemetrexed plus Carboplatin or Cisplatin; Subjects randomized to the control group received pemetrexed 500 mg/m² + platinum-based chemotherapy (carboplatin AUC 5 or cisplatin 75 mg/m²) via intravenous infusion for 4-6 cycles (determined by the investigator) as initial therapy, followed by pemetrexed maintenance therapy (500 mg/m²) until disease progression, intolerable toxicity, initiation of new antitumor therapy, death, loss to follow-up, or other treatment-terminating conditions (whichever occurred first).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) by BICR	Progression-free survival (PFS) as assessed by a Blind Independent Center Review Committee (BICR) with reference to RECIST v1.1 for Solid tumors.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the date of the first dose until the date of death due to any cause.	3 years
Progression-Free Survival (PFS) by the investigator	Refer to RECIST v1.1, PFS assessed by the investigator.	2 years
The objective response rate of the tumor (ORR)	Refer to RECIST v1.1, ORR assessed by the investigator and BICR.	2 years
Duration of Response (DoR)	Refer to RECIST v1.1, DoR assessed by the investigator and BICR.	2 years
The disease control rate (DCR)	Refer to RECIST v1.1, DCR assessed by the investigator and BICR.	2 years
Objective Response Rate (ORR) in subjects with baseline intracranial metastases	Refer to RECIST v1.1，ORR assessed by the investigator and BICR.	2 years
The Disease Control Rate (DCR) in subjects with baseline intracranial metastases	Refer to RECIST v1.1, DCR assessed by the investigator and BICR.	2 years
Duration of Response (DoR) in subjects with baseline intracranial metastases	Refer to RECIST v1.1, DoR assessed by the investigator and BICR.	2 years
Progression-Free Survival (PFS) in subjects with baseline intracranial metastases	Refer to RECIST v1.1, PFS assessed by the investigator and BICR.	2 years
Incidence of Treatment-Emergent Adverse Events	Incidence of Treatment-Emergent Adverse Events (TEAEs),A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.	2 years
Plasma concentrations of Vebreltinib and PLB1004	Plasma concentrations of Vebreltinib and PLB1004.	2 years
Second progression-free survival (PFS2)	Investigator-assessed second progression-free survival (PFS2).	2 years
Assess the Quality of Healthy Living About Patients（EQ-5D-5L）	Use the EQ-5D-5L scale to measure patients' quality of healthy living. It has 5 items (Mobility, Self-care, Usual activities, Pain/discomfort, Depression/anxiety). Each item contains 5 levels: 1= no difficulty, 2= slight difficulty, 3= moderate difficulty, 4= serious difficulty, 5= extremely serious difficulty. The higher the score has the worse the health. Then, the score calculation of the European Five-Dimensional Health Scale is based on the calculation formula published by the EuroQol Group. Based on 5 combinations of different severity levels, a score of 0 to 1 is obtained. 0 is the least healthy and 1 is the most healthy.	2 years

Collaborators and Investigators

• Sponsor: Avistone Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 25, 2025
• First Submitted That Met QC Criteria: May 6, 2025
• First Posted (Actual): May 14, 2025

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Lung Cancer; NSCLC; EGFR; EGFR L858R; MET Amplification; EGFR Exon 19 Deletion
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Pemetrexed; Carboplatin
• Other Study ID Numbers: PLB1001/PLB1004-NSCLC-III-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No