Combination of Vebreltinib and Osimertinib in Patients with EGFR 21 L858R Mutation Advanced NSCLC

An Open-label, Single-center, Single-arm Phase IIa Study to Evaluate the Safety and Efficacy of Vebreltinib in Combination with Osimertinib in Patients with Locally Advanced or Metastatic Non-small Cell Lung Cancer with EGFR 21 L858R Mutation

This is a Prospective, open label, single arm study to evaluate the efficacy and safety of Vebreltinib combined with Osimertinib in the treatment of locally advanced or metastatic non-small cell lung cancer with EGFR 21 L858R mutation

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: Vebreltinib; Drug: Osimertinib

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Cancer insititue and Hospital of CHINESE ACADEMY OF MEDICAL SCIENCE

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Signed an informed consent form.

  2. Patients aged ≥18.

  3. Histologically or cytologically confirmed locally or metastatic NSCLC.

  4.EGFR 21 L858R mutation.

  5.at least one measurable lesion according to RECIST 1.1 criteria.

  6.ECOG PS 0-1.

  7.appropriate organ function.

  8.For female subjects of reproductive age, a urine or serum pregnancy test should be performed negative within 7 days prior to receiving the first study drug administration .If there is a risk of conception, all subjects (male or female) must agree to use effective contraception from the time they sign an informed consent until 3 months after the final administration of the study drug.

  9.The expected survival is more than 3 months.

Exclusion Criteria:

• 1.Patients with EGFR 19del mutation , ALK or ROS1 gene fusions.

  2. Patients with symptomatic, neurologically unstable central nervous system (CNS) metastases, or CNS diseases that require increased steroid doses to control.

  3. Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.

  4.Previous treatment history meets one of the following criteria: 1)prior treated with systemic treatment. 2)The last administration of other anti-tumor drugs was less than 14 days or 5 half-life period before the initiation of study agents. 3)Received traditional Chinese medicine with anti-tumor indications within 1 week prior to initiation of treatment, 4)Thoracic radiotherapy to lung fields (including whole brain radiotherapy) ≤4 weeks prior to initiation of study treatment , for all other sites (except lung and whole brain) ≤2 weeks prior to initiation of study treatment. 5)Received major surgery within the past 4 weeks, or received resection of brain metastatic lesion within 2 weeks, or the side effects of such surgery have not yet been recovered.

  5.Previous anti-tumor therapy toxicity have not been recovered to ≤ Grade 1 (NCI-CTCAE 5.0) or baseline, except for alopecia, skin pigmentation and grade 2 peripheral neurotoxicity.

  6.Receive a potent inducer and/or potent inhibitor of CYP3A4 within 1 week prior to initiation of study drug or need receive a potent inducer and/or potent inhibitor of CYP3A4 during the study period.

  7.Any serious or uncontrolled systemic disease, including, but not limited to, other serious or psychiatric disorders or laboratory abnormalities, in which the investigator determines that the study drug is not suitable for the patient or affects protocol adherence.

  8.Cardiac function and disease meet one of the following criterias: QTc > 470 ms, Severe cardiac arrhythmia; Any risk factors that increase the length of the QTc; New York College of Cardiology (NYHA) Heart function grade ≥3. Poorly controlled hypertension.

  9.Have a history of interstitial lung disease, drug-induced interstitial lung disease, or radiation pneumonia requiring steroid therapy, or are currently receiving drug therapy or other clinical interventions, or have existing active interstitial lung disease.

  10.A history of thromboembolic or venous thromboembolic events (including myocardial infarction, cerebrovascular event or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other severe thromboembolic event) in the 6 months prior to the initial study drug administration, Any life-threatening bleeding event (including treatment requiring blood transfusion, surgery or local treatment, and ongoing medication) was judged to have a bleeding tendency.

  11.Active gastrointestinal disorders (such as ulcerative lesions, uncontrolled nausea, vomiting, diarrhea, and malabsorption syndrome) or other conditions (such as inability to swallow the investigational agent, or prior major gastrointestinal surgery) may significantly affect the absorption, distribution, metabolism, or excretion of the oral investigational agent.

  12.Patients with poorly controlled pleural effusion, peritoneal effusion, or pericardial effusion were judged by the investigators to be unsuitable for inclusion.

  13.Any systemic disease that the investigator determines to require treatment .

  14.A history of acute or chronic pancreatitis, pancreatic surgery, or risk factors that may increase the risk of developing pancreatitis.

  15.Active infection, including but not limited to:infected with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) (HIV antibody positive), infected with syphilis, active tuberculosis, the presence of active infections (such as pneumonia) requiring systematic anti-infective therapy within 2 weeks before drug administration in the first study.

  16.Patients being treated with warfarin or any other anticoagulant, except low-dose warfarin (< 2 mg) for the prevention of central catheter-associated thrombosis;

  17.Participants with known hypersensitivity or contraindications to study drug of same class or any excipient of these agents.

  18.Pregnant or lactating women.

  19.Patients were currently enrolled in another clinical study or received another clinical study drug within 2 weeks prior to initiation of study treatment.

  20. Other circumstances that, in the judgment of the investigator, may affect the conduct of the clinical study and the determination of the results of the study or increase the risks associated with drug administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm; All patients received oral Vebreltinib 100mg BID plus Osimertinib 80mg once daily.	Drug: Vebreltinib; Vebreltinib 100mg oral BID; Other Names: Bozitinib; PLB1001; Drug: Osimertinib; Osimertinib 80mg oral once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	From the first treatment to the date of first documentation of disease progression, or death due to any cause	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From the first administration to death from any cause	5 years
Overall Response Rate	ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1.	3 years
Duration of Response	DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator or death in the absence of disease progression.	3 years
Incidence of Treatment-Emergent Adverse Events	A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.	3 years

Collaborators and Investigators

• Sponsor: National Cancer Center, China
• Collaborators: Avistone Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: February 10, 2025
• First Submitted That Met QC Criteria: February 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; EGFR; Vebreltinib
• 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; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: NCC4728

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
• product manufactured in and exported from the U.S.: No