Efficacy and Safety Evaluation of PLB1004 in Patients With Non-squamous NSCLC Harboring EGFR Exon 20 Insertion.
- Conditions
- Non-Small-Cell Lung Cancer
- Interventions
- Registration Number
- NCT06281964
- Lead Sponsor
- Avistone Biotechnology Co., Ltd.
- Brief Summary
Efficacy and safety evaluation of PLB1004 in patients with locally advanced/metastatic non-squamous NSCLCharboring EGFR exon 20 insertion.
- Detailed Description
Randomized, controlled, open label, multicenter phase III study to evaluate the efficacy and safety of PLB1004 Versus platinum-based chemotherapy with or without Sintilimab in the first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) Exon 20 insertion(ex 20) mutations.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 327
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Ability to understand and willingness to sign a written informed consent document.
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Aged at least 18 years old.
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Histologically or cytologically confirmed locally advanced or metastatic NSCLC (stage IIIB~IV).
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Tumor tissue has written confirmation of EGFR by second generation sequencing (NGS) testing by a local laboratory or sponsor designated central laboratory accredited by the Clinical Laboratory Improvement Act Amendments (CLIA), International Organization for Standardization/Independent Ethics Committee (ISO/IEC), College of American Pathologists (CAP) (or other equivalent accreditation) Ex20ins is positive. Note: Considering that there are multiple subtypes of EGFR Ex20ins, the mutant subtypes to be included in the subjects should be representative and reflect the epidemiological distribution characteristics。Participants with EGFR ex20ins mutation.
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At least one measurable lesion as defined by RECISTV1.1（Brain lesions were not included in measurable target lesions）
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ECOG performance status 0 to 1.
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Life expectancy is not less than 12 weeks.
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No previous systemic treatment for locally advanced or metastatic non-squamous cell cancer NSCLC. Note: Subjects are allowed to receive neoadjuvant/adjuvant therapy as long as the relevant therapy has ended at least 6 months before the disease is diagnosed as locally progressive or metastatic tumors
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Have one of the following previous anti-tumor treatments: prior to the first dose of PLB1004
a) Any anti-EGFR TKI for the EGFR ex20ins mutation.. b) Received Chinese patent drugs with anti-tumor indications within 1 week before administration of the first study drugReceived Chinese patent drugs with anti-tumor indications within 1 week before administration of the first study drug c) required administration of the multidrug and toxin efflux protein (MATE) transporter substrate metformin within 1 week before and during the first study drug administration d）Strong inhibitors or strong inducers of the cytochrome P450 3A4 enzyme (CYP3A4) were required within 1 week before and during the study e) required immunosuppressive medication within 2 weeks before or during the first dose of study drug f) Major surgery within 4 weeks prior to starting PLB1004 or who have not recovered from side effects of such procedure except for the biopsy of Thoracoscopy and the clinical test of Mediastinoscopy could ≤ 7 days prior to starting PLB1004 g) Radiotherapy to lung fields and whole-brain fields ≤4 weeks prior to starting PLB1004. For all other anatomic sites, radiotherapy ≤2 weeks prior to starting PLB1004 or patients who have not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions is not included.
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Patients with spinal cord compression ,brain membrane metastasis and symptomatic central nervous system (CNS), who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study manage CNS symptoms.
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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
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Did not recover from any toxicity and/or complications of previous anti-cancer treatments such as chemotherapy, surgery, and radiotherapy, 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 alopecia and irrecoverable permanent radiation damage
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A tendency to coagulopathy or bleeding, including an arterial or venous thromboembolic event (including a history of myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other major thromboembolism) within 6 months before randomization; Any life-threatening bleeding event (including the need for blood transfusion, surgical or local treatment, or continued medical therapy) or major vascular invasion was considered by the investigator to be bleeding prone
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Severe cardiac disease, such as any serious arrhythmia (including ventricular arrhythmia, drug-refractory supraventricular and other arrhythmias), grade III or higher cardiac dysfunction (New York Heart Association [NYHA], see Appendix 4 for details), and left ventricular ejection fraction (LVEF) <50% on echocardiography;
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Mean corrected QT intervals (QTcF) of three electrocardiograms during screening, calculated according to Fridericia's formula at rest, were >470 ms;
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Presence of uncontrolled hypertension (treated systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg)
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Dysphagia, or active digestive disease or major gastrointestinal surgery that may affect the administration or absorption of the study drug (e.g., ulcerative lesions, uncontrolled nausea, vomiting, diarrhea, and malabsorption syndromes);
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Allergy or intolerance to the drug class and excipient components of the study drug
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pregnant or nursing women.
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Received live vaccine within 4 weeks before randomization;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description platinum-based chemotherapy with or without Sintilimab Pemetrexed+（carboplatin or Cisplatin）with or without Sintilimab platinum-based chemotherapy with or without Sintilimab PLB1004 PLB1004 PLB1004 given alone as monotherapy
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) by BICR 3 years Progression-free survival (PFS) as assessed by a Blind Independent Center Review Committee (BICR) with reference to RECIST v1.1 for Solid tumors
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) 3 years DOR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first.
Disease Control Rate (DCR) 3 years DCR is defined as the percentage of participants achieving complete or partial response or stable disease as defined per RECIST v 1.1
Plasma concentrations of PLB1004 and metabolites may be combined with data from other clinical studies 3 years Plasma concentrations of PLB1004 and metabolites may be combined with data from other clinical studies
Progression-Free Survival (PFS) by the investigator 2 years Refer to RECIST v1.1, PFS assessed by the investigator
Intracranial Overall Response Rate（ORR） 3 years To evaluate the intracranial Overall Response Rate（ORR）which is defined by investigator as the proportion of subjects with Intracranial disease confirmed best overall response of complete response or partial response per RECIST v 1.1.
Overall Survival (OS) 3 years OS is defined as the time from the date of the first dose until the date of death due to any cause.
Incidence of Treatment-Emergent Adverse Events (TEAEs) 3 years A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug assessed by CTCAE v5.0