A Confirmatory Clinical Study in NSCLC Patients With MET Exon 14 Mutation (KUNPENG-2)

NCT05989542 | Recruiting Phase 3

• 1 other identifier: PLB1001-IIIb-NSCLC-01
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test if PLB1001 works well and safely in Non-small cell lung cancer patients with MET exon 14 mutation. The main questions it aims to answer are:

• If it is works well in Non-small cell lung cancer patients with MET exon 14 mutation
• If it is safety and tolerant in Non-small cell lung cancer patients with MET exon 14 mutation Participants will
• be given PLB1001 200mg BID,oral.
• be received hematology and urine and ECG examinations every 14 days (First 3 months) or every 28 days (After 3 months)
• be received Image examination every 8 weeks(First year) or every 12 weeks(After one year)

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Confirmed Objective Response Rate Evaluated by IRC

  Objective response rate will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Objective response rate is defined as the percentage of patients who experienced either a complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, but at least increase 5mm, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  2 years

Secondary Outcomes (10)

• Confirmed Objective Response Rate evaluated by Investigator

  2 years

• Disease Control Rate evaluated by IRC and Investigator

  2 years

• Duration Of Response evaluated by IRC and Investigator

  2 years

• Time To Response evaluated by IRC and Investigator

  2 years

• Progression Free Survival evaluated by IRC and Investigator

  2 years

Other Outcomes (1)

• Minimum plasma concentration (Cmin) of drug and safety-analysis-set.etc

  Within 2 hours prior to morning dose on day 1 (±7) of Cycle 2,Cycle,3,Cycle5 (eash cycle is 28 days )

Study Arms (1)

PLB1001

EXPERIMENTAL

Subjects will receive 200mg of PLB1001 twice daily in cycles of 28-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.

Drug: PLB1001

Interventions

PLB1001 DRUG

200mg BID Oral

PLB1001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• voluntarily sign a written informed consent to participate in the study and be willing and able to comply with study-related visits and procedures;
• Male or female aged 18 years and above;
• patients with histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (including sarcomatoid carcinoma of the lung, according to the AJCC 8th edition of lung cancer staging, Stage IIIB - Stage IV) (non-site pathology reports are acceptable);Patients have not received any prior systemic antineoplastic drug therapy for advanced diseaseor disease progression or toxicity intolerance after prior systemic therapy (≤3 lines);
• The presence of MET exon 14 jump mutation was confirmed by the NGS test in the central laboratory, and the 'Combined Human 9 Gene Mutation Detection Kit (Reversible End Termination Sequencing)' produced by Guangzhou Burning Stone Medical Laboratory Ltd. will be used for the testing and analysis of the samples in the central laboratory. Patients are required to provide sufficient blood samples for retrospective analysis by the central laboratory ('Human Circulating Tumour DNA Multi-Gene Mutation Test Kit (Reversible End Termination Sequencing Method)' manufactured by Guangzhou Burnstone Medical Laboratory Co. Ltd. to support the development of blood companion diagnostic reagents required for the marketing of Piratinib. Note: For patients who have received previous systemic anti-tumour therapy, tumour tissue obtained after disease progression on the most recent anti-tumour therapy will be preferred for biomarker testing;
• Tissue sample testing confirms EGFR wild-type, ALK rearrangement negative, ROS1 rearrangement negative, and KRAS mutation negative;
• at least one measurable lesion (per RECIST 1.1 criteria). For a lesion that has received prior radiotherapy, it may be counted as a target lesion only if definitive disease progression has occurred since radiotherapy;
• an ECOG performance status score of 0-1;
• expected survival ≥ 3 months;
• Laboratory tests that meet the following requirements:
• Aspartate aminotransferase (AST): ≤ 3 x ULN (no liver metastases)
• Alanine aminotransferase (ALT): ≤3 × ULN (no liver metastases)
• Total bilirubin (TBIL): ≤1.5 × ULN (no liver metastases)
• AST: ≤5.0 × ULN (with liver metastases)
• ALT: ≤5.0 × ULN (with liver metastasis)
• Total bilirubin: ≤3.0 × ULN (with liver metastases)

You may not qualify if:

• unwilling to provide tumor tissue or blood samples for molecular testing;
• previous treatment with MET inhibitors or HGF-targeted therapy;
• have symptomatic and neurologically unstable central nervous system (CNS) metastases or CNS disease that requires increased steroid doses for control; NOTE: Patients with CNS metastases whose symptoms have been controlled may be enrolled in this trial. Patients with symptomatic or unstable CNS metastases must have completed radiotherapy, or at least 2 weeks after surgical treatment of CNS tumor metastases, prior to study entry. Patients must have stable neurologic function with no new neurologic deficits identified on clinical examination and no new problems identified on CNS imaging. If the patient requires steroids for the treatment of CNS metastases, they must have been stabilized on a therapeutic dose of steroids for at least 2 weeks prior to signing the informed consent form;
• patients with clinically poorly controlled pleural, abdominal or pericardial effusions who, in the judgment of the investigator, are not suitable for enrollment;
• unstable or uncontrolled disease or conditions related to or affecting cardiac function (e.g., unstable angina pectoris, congestive heart failure \[NYHA \> Class II\], unstably controlled hypertension \[defined as diastolic blood pressure \> 100 mmHg and/or systolic blood pressure \> 160 mmHg regardless of antihypertensive medications. initiation of antihypertensive medications or adjustment of antihypertensive medications prior to Screening is permitted\]);
• a coagulation disorder or bleeding tendency, including an arterial or venous thromboembolic event (including myocardial infarction, cerebrovascular accident or transient ischemic attack, pulmonary artery embolism, deep vein thrombosis, or any other history of severe thromboembolism) within 6 months prior to the administration of the first study medication, any life-threatening bleeding event (including the need for transfusional therapy, surgical or topical therapy, and ongoing drug therapy) that Tendency to bleed in the judgment of the investigator;
• The presence of risk factors for QTc interval prolongation such as chronic hypokalaemia not corrected by complementary therapies, congenital or familial long QT interval syndrome, family history of unexplained sudden death in a first-degree relative under the age of 40 years, or initiation of Piratinib. Patients with a family history of unexplained sudden death in a first-degree relative younger than 40 years of age, or use of a drug that prolongs the QT interval and results in tip-twist ventricular tachycardia for ≤5 half-lives prior to the initiation of the first dose of ponatinib should be excluded.
• Patients with ≤5 half-lives of drugs that prolong the QT interval and cause tip-twist ventricular tachycardia prior to initiation of Brentinib should be excluded.
• any significant rhythm abnormality such as complete left bundle branch block, second or third degree heart block, medically uncontrolled ventricular arrhythmias, supraventricular, nodal arrhythmias, and medically uncontrolled other cardiac arrhythmias;
• active gastrointestinal disorders (e.g., ulcerative lesions, uncontrollable nausea, vomiting, diarrhea, and malabsorption syndromes) or other conditions (e.g., inability to swallow the test medication, or prior major gastrointestinal surgery) that significantly interfere with absorption, distribution, metabolism, or excretion of the oral study drug;
• the presence of an active infection, including but not limited to: 1) Hepatitis B (Hepatitis B Surface Antigen \[HBsAg\] positive and Hepatitis B Virus \[HBV\] DNA ≥ 500 IU/ml), Hepatitis C (positive for both anti-Hepatitis C Virus \[HCV\] antibodies and HCV-RNA) or Human Immunodeficiency Virus (HIV) (HIV antibody positive) infections, and syphilis positive infections; 2) Active tuberculosis; 3) Active infection (e.g., pneumonia) requiring systemic anti-infective therapy within 2 weeks prior to first study drug administration;
• known history of hypersensitivity to the active or inactive excipients of Vebreltinib, hypersensitivity to drugs with a chemical structure similar to that of Vebreltinib.
• patients being treated with warfarin or any other coumarin derivative anticoagulant, with the exception of low-dose warfarin (\< 2 mg) for the prevention of central catheter-related thrombosis;
• presence of prior antineoplastic therapy toxicity not recovered to ≤ Grade 1 (NCI-CTCAE 5.0) or baseline, except for alopecia, skin hyperpigmentation, and Grade 2 peripheral neurotoxicity
• any comorbid medical condition that may increase the risk of toxicity;

Sponsors & Collaborators

• Beijing Pearl Biotechnology Limited Liability Company: lead

Study Sites (1)

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510080, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yilong Wu, MD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weizhe Xue, Ph.D

CONTACT

+86-10-84148931; xueweizhe@pearlbio.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2023
• First Posted: August 14, 2023
• Study Start: October 16, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)