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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 (PYRAMID-1)

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ClinicalTrials.gov Identifier: NCT04447118
Recruitment Status : Recruiting
First Posted : June 25, 2020
Last Update Posted : March 25, 2021
Sponsor:
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-squamous NSCLC HER2 Exon 20 Mutation Drug: Pyrotinib Drug: Docetaxel Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: In this study, the Blinded Independent Review Committee (BIRC) will perform a blinded evaluation on the primary endpoint.
Primary Purpose: Treatment
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
Actual Study Start Date : September 11, 2020
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : October 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: Study treatment Arm
Pyrotinib maleate tablet, 400 mg, once daily (QD)
Drug: Pyrotinib
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.
Other Name: Irene

Active Comparator: Control Arm
Docetaxel injection, 75 mg/m2, once every 3 weeks (Q3W)
Drug: Docetaxel
75 mg/m2, once every 3 weeks (Q3W), will be administered by intravenous infusion over 1 hour, with 21 days as a cycle.
Other Name: Docetaxel injection




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 26 months ]
    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 :
  1. Overall survival (OS) [ Time Frame: 36 months ]
    Time from the date of randomization to death for any cause.

  2. Objective response rate (ORR) [ Time Frame: 26 months ]
    Assessed by BIRC and investigator according to the RECIST v1.1.

  3. Disease control rate (DCR) [ Time Frame: 26 months ]
    Assessed by BIRC and investigator according to the RECIST v1.1.

  4. Duration of response (DoR) [ Time Frame: 26 months ]
    Assessed by BIRC and investigator according to the RECIST v1.1.

  5. Time to tumor progression (TTP) [ Time Frame: 26 months ]
    Assessed by BIRC and investigator according to the RECIST v1.1.

  6. Progression-free survival 2(PFS2) [ Time Frame: 36 months ]
    Assessed by investigator according to the RECIST v1.1, or death for any cause, whichever comes first.

  7. Patient reported outcome (PRO) using EORTC QLQ-C30 [ Time Frame: 26 months ]
    Symptoms related to NSCLC,

  8. Patient reported outcomes (PRO) using the QLQ-LC13 [ Time Frame: 26 months ]
    Symptoms related to NSCLC

  9. Plasma concentrations of pyrotinib [ Time Frame: 26 months ]
    Pharmacokinetics (PK) of pyrotinib

  10. AEs and SAEs [ Time Frame: 26 months ]
    Judged in accordance with NCI-CTCAE v5.0



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04447118


Contacts
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Contact: Caixun Zhou, MD,PhD 86-021-65115006 ext 3050 caicunzhoudr@163.com
Contact: Huiyu Lan +86 15000239047 lanhuiyu@hrglobe.cn

Locations
Show Show 54 study locations
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Investigators
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Study Director: Wei Shi, MD,PhD Jiangsu HengRui Medicine Co., Ltd.
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Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier: NCT04447118    
Other Study ID Numbers: HR-BLTN-III-NSCLC
First Posted: June 25, 2020    Key Record Dates
Last Update Posted: March 25, 2021
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jiangsu HengRui Medicine Co., Ltd.:
pyrotinib
docetaxel
HER2 Exon 20 Mutation
NSCLC
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action