Phase 3 Study of Pyrotinib Versus Docetaxel in Patients With Advanced Non-squamous NSCLC Harboring a HER2 Exon 20 Mutation Who Failed Platinum Based Chemotherapy

Study Overview
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Brief Summary
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This is a randomized, positive-controlled, open-label, international multicenter, Phase 3 clinical study to compare the efficacy and safety of pyrotinib versus docetaxel in patients with advanced non-squamous NSCLC harboring a HER2 exon 20 mutation who failed platinum based chemotherapy.

Detailed Description
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150 eligible subjects will be randomized in a 2:1 ratio (Study treatment Arm: Control Arm = 100 : 50 subjects) to receive pyrotinib or docetaxel monotherapy. Each treatment cycle is defined as 21 days for subjects in both arms. Treatment regimen of pyrotinib (Study treatment Arm): 400 mg/d (QD) oral pyrotinib will be administered within 30 minutes after completion of a meal. Treatment regimen of docetaxel (Control Arm): 75 mg/m2 (Q3W) of docetaxel will be administered via intravenous infusion. In this study, crossover treatment is allowed for subjects in Control Arm. Within the specified time window of each cycle, subjects should complete physical examinations, laboratory tests, quality of life questionnaires and other tests to assess the safety and quality of life of the subjects. During study treatment, tumor radiological assessments will be performed every 6 weeks (42 ± 7 days) in the first 52 weeks and every 12 weeks (84 ± 7 days) thereafter. After the end of treatment and safety follow-up, all subjects will be followed for survival (every 56 ± 7 days) until death, withdrawal of informed consent, lost to follow-up, or termination of the study (whichever occurs first).

Official Title
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A Phase 3, Randomized, Open-label, Multicenter Study of the Efficacy and Safety of Pyrotinib Versus Docetaxel in Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC) Harboring a HER2 Exon 20 Mutation Who Progressed on or After Treatment With Platinum Based Chemotherapy

Conditions
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Non-squamous NSCLC, HER2 Exon 20 Mutation

Intervention / Treatment
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* Drug: Pyrotinib
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written informed consent which is approved by IRB/EC, willing and able to comply with scheduled treatment, all examinations at study visits, and other study procedures. ECOG PS 0-1. Have histologically or cytologically confirmed locally advanced or metastatic non-squamous NSCLC disease. Before enrollment, a documented confirmed presence of activating mutations in exon 20 of the HER2 gene must be provided. Sufficient tumor tissue samples should be provided to retrospectively confirm the mutation status of the HER2 gene. Must have measureable disease per RECIST v1.1. For advanced NSCLC, patients must have had progressive disease on or after a platinum based chemotherapy, with or without immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) and/or anti-angiogenic drugs. No more than 2 prior lines of systemic therapy are allowed. The laboratory test values must meet the following standards to manifest that the functional level of important organs/systems meets the requirements. Female patient of childbearing potential (WOCBP) and male patient whose - partner is WOCBP must agree to use effective contraception method during the study period. Exclusion Criteria: Malignant tumors with other pathological types. Medical history of other active malignancies within last 5 years. Subjects with active CNS metastases. Previously treated with targeted drugs for HER2 gene mutations,or previously treated with docetaxel. Prior to the first dose of study treatment, patients with severe effusions with clinical symptoms, severe cardiac disease, or severe infection. Prior to the first dose of study treatment, patients with diseases or special conditions that affect drug administration and absorption. Congenital or acquired immunodeficiency. History of allergy to the study drugs or components. Prior to the first dose of study treatment, or during the study period, patients receive or are anticipated to receive continuous strong CYP3A4 inducers or inhibitors, P-gp inhibitors, or medications that are known to cause QT/QTc prolongation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study treatment Arm<br>Pyrotinib maleate tablet, 400 mg, once daily (QD) | Drug: Pyrotinib<br>* 400 mg, once daily (QD), will be administered with water within 30 minutes after completion of a meal, at approximately the same time each day on a continuous daily dosing schedule, with 21 days as a cycle.<br>* Other names: Irene;|
| Active Comparator: Control Arm<br>Docetaxel injection, 75 mg/m2, once every 3 weeks (Q3W) | Drug: Docetaxel<br>* 75 mg/m2, once every 3 weeks (Q3W), will be administered by intravenous infusion over 1 hour, with 21 days as a cycle.<br>* Other names: Docetaxel injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Time from the date of randomization to the date of first disease progression documented by BIRC according to the RECIST v1.1 or death for any cause, whichever comes first. | 26 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Time from the date of randomization to death for any cause. | 36 months | 
| Objective response rate (ORR) | Assessed by BIRC and investigator according to the RECIST v1.1. | 26 months | 
| Disease control rate (DCR) | Assessed by BIRC and investigator according to the RECIST v1.1. | 26 months | 
| Duration of response (DoR) | Assessed by BIRC and investigator according to the RECIST v1.1. | 26 months | 
| Time to tumor progression (TTP) | Assessed by BIRC and investigator according to the RECIST v1.1. | 26 months | 
| Progression-free survival 2(PFS2) | Assessed by investigator according to the RECIST v1.1, or death for any cause, whichever comes first. | 36 months | 
| Patient reported outcome (PRO) using EORTC QLQ-C30 | Symptoms related to NSCLC, | 26 months | 
| Patient reported outcomes (PRO) using the QLQ-LC13 | Symptoms related to NSCLC | 26 months | 
| Plasma concentrations of pyrotinib | Pharmacokinetics (PK) of pyrotinib | 26 months | 
| AEs and SAEs | Judged in accordance with NCI-CTCAE v5.0 | 26 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pyrotinib, docetaxel, HER2 Exon 20 Mutation, NSCLC