Clinical Trials /

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

NCT04447118

Description:

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.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: HR-BLTN-III-NSCLC
  • NCT ID: NCT04447118

Conditions

  • Non-squamous NSCLC
  • HER2 Exon 20 Mutation

Interventions

DrugSynonymsArms
PyrotinibIreneStudy treatment Arm
DocetaxelDocetaxel injectionControl Arm

Purpose

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

      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).
    

Trial Arms

NameTypeDescriptionInterventions
Study treatment ArmExperimentalPyrotinib maleate tablet, 400 mg, once daily (QD)
  • Pyrotinib
Control ArmActive ComparatorDocetaxel injection, 75 mg/m2, once every 3 weeks (Q3W)
  • Docetaxel

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:26 months
Safety Issue:
Description: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.

Secondary Outcome Measures

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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jiangsu HengRui Medicine Co., Ltd.

Trial Keywords

  • pyrotinib
  • docetaxel
  • HER2 Exon 20 Mutation
  • NSCLC

Last Updated

December 8, 2020