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)

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

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.

Study Overview

• Status: Completed
• Conditions: Non-squamous NSCLC; HER2 Exon 20 Mutation
• Intervention / Treatment: Drug: Pyrotinib; Drug: Docetaxel

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).

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Albury, Australia
    • Border Medical Oncology
  • Fitzroy, Australia
    • St Vincent's Hospital Melbourne
  • Nedlands, Australia
    • Sir Charles Gairdner Hospital
  • North Adelaide, Australia
    • Calvary North Adelaide Hospital
  • Saint Leonards
    • St Leonards, Saint Leonards, Australia
      • Royal North Shore Hospital
• Belgium
  • Edegem, Belgium
    • Antwerp University Hospital (UZA)
  • Ghent, Belgium
    • University Hospital Gent
  • Leuven, Belgium
    • University Hospital (UZ) Leuven
• China
  • Anhui
    • Hefei, Anhui, China
      • The Second Affiliated Hospital of Anhui Medical University
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Peking University Cancer Hospital
    • Beijing, Beijing Municipality, China
      • Beijing Chest Hospital,Capital Medical University
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • The Second Affiliated Hospital of Chongqing Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Guangdong Pharmaceutical University
  • Hebei
    • Cangzhou, Hebei, China
      • Cangzhou Hospital of Integrated Tcm-Wm.Hebei
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China
      • First Affiliated Hospital of ZhengzhouUniversity
  • Hubei
    • Wuhan, Hubei, China
      • Hubei cancer hospital WardII
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Cancer Hospital
    • Yangzhou, Jiangsu, China
      • Subei People's Hospital of Jiangsu province
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The Second Affiliated of Nanchang University
  • Jilin
    • Changchun, Jilin, China
      • Jilin Cancer Hospital
  • Neimenggu
    • Hohhot, Neimenggu, China
      • The affiliated hospital of inner mongolia medical univerity
  • Shandong
    • Jinan, Shandong, China
      • Shandong Cancer Hospital Affiliated to Shandong University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai Chest Hospital
    • Shanghai, Shanghai Municipality, China, 200433
      • Shanghai pulmonary hospital, Tongji University
    • Shanghai, Shanghai Municipality, China
      • Fudan University Cancer Hospital
    • Shanghai, Shanghai Municipality, China
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China
      • Shanxi Provincial Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • Sichuan Cancer Hospital
    • Chengdu, Sichuan, China
      • West China Hospital,Sichuan University
    • Yibin, Sichuan, China
      • The Second People's Hosipital of Yibin
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • General Hospital of Tianjin Medical University
  • Yunnan
    • Kunming, Yunnan, China
      • Yunnan Provincial Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital,Zhejiang University
    • Taizhou, Zhejiang, China
      • Taizhou Hospital of Zhejiang Province
• France
  • Caen, France
    • Centre Francois Baclesse
  • Créteil, France
    • Centre Hospitalier Intercommunal Creteil
  • Marseille, France
    • AP-HM - Hôpital Nord
  • Paris, France
    • Hopital Bichat - Claude Bernard - AP-HP
  • Strasbourg, France
    • CHRU Strasbourg
  • Toulouse, France
    • CHU Toulouse - Hopital Larrey
• Germany
  • Dresden, Germany
    • Universitaetsklinikum Carl Gustav Carus Dresden
  • Giessen, Germany
    • Uniklinikum Gießen und Marburg
  • Kempten, Germany
    • Klinikverbund Kempten-Oberallgäu gGmbH
  • Leipzig, Germany
    • POIS Leipzig GbR
  • Oldenburg, Germany
    • Pius-Hospital Oldenburg, Centre of Radiotherapy and Medical Oncology, Dept. Medical Oncology
• Italy
  • Aviano, Italy
    • Centro Riferimento Oncologico - Aviano
  • Catania, Italy
    • Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico
  • Meldola (FC), Italy
    • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
  • Milan, Italy
    • Istituto Europeo di Oncologia
  • Varese, Italy
    • ASST dei Sette Laghi-Ospedale di Circolo e Fondazione Macchi di Varese
• Poland
  • Konin, Poland
    • Centrum Onkologii KOMED
  • Lodz, Poland
    • Salve-Medica
  • Lublin, Poland
    • Instytut Genetyki i Immunologii GENIM
  • Poznan, Poland
    • Med Polonia Sp. z o.o.
• Russia
  • Arkhangelsk, Russia
    • Arkhangelsk Clinical Oncological Dispensary
  • Moscow, Russia
    • JSC Group of companies Medsi
  • Saint Petersburg, Russia
    • Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
  • Saint Petersburg, Russia
    • Clinical hospital RZD-Medicine of St. Petersburg
  • Saint Petersburg, Russia
    • Eurocityclinic LLC
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia
      • Petrov National Medical Research Center of Oncology
• South Korea
  • Gyeonggi-do, South Korea
    • Ajou University Hospital
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Korea University Anam Hospital
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea
    • Seoul St. Mary's Hospital, The Catholic University of Korea
  • Bundang
    • Seoul, Bundang, South Korea
      • Seoul National University Bundang Hospital
• Spain
  • Barcelona, Spain
    • Hospital Clinic Barcelona
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Fundación Jiménez Díaz
  • Málaga, Spain
    • Hospital Regional Universitario de Malaga
  • Pamplona, Spain
    • Complejo Hospitalario de Navarra
  • Seville, Spain
    • Hospital Universitario Virgen del Rocío
  • Valencia, Spain
    • Instituto Valenciano de Oncología
  • Badalona
    • Barcelona, Badalona, Spain
      • Hospital Germans Trias I Pujol
    • Barcelona, Badalona, Spain
      • Hospital Universitario Vall d'Hebron
• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan
    • Linkou Chang Gung Memorial Hospital (CGMHLK)
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye)
    • Baskent University Adana Application and Research Center
  • Ankara, Turkey (Türkiye)
    • Ankara Sehir Hastanesi
  • Istanbul, Turkey (Türkiye)
    • Istanbul University Cerrahpasa Medical Faculty
  • Izmir, Turkey (Türkiye)
    • Izmir Medical Park Hospital
  • Keçiören, Turkey (Türkiye)
    • Gulhane Training and Research Hospital
  • Konya, Turkey (Türkiye)
    • Necmettin Erbakan University Selcuklu Faculty of Medicine
  • Merkez, Turkey (Türkiye)
    • Trakya University Medical Faculty
• United States
  • California
    • Orange, California, United States, 92868
      • University of California - Irvine Medical Center
    • Sacramento, California, United States, 95817
      • University of California (UC) Davis Comprehensive Cancer Center
    • Whittier, California, United States, 33756
      • Innovative Clinical Research Institute
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists South Divisio
    • St. Petersburg, Florida, United States, 33701
      • Florida Cancer Specialists North Divisio
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center (KUMC)
  • New York
    • New York, New York, United States, 10021
      • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 33756
      • Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center
  • Washington
    • Spokane, Washington, United States, 99208
      • Summit Cancer Centers - North Spokane

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Docetaxel injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Study Director: Wei Shi, MD,PhD, Jiangsu Hengrui Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2020
• Primary Completion (Actual): June 2, 2023
• Study Completion (Actual): December 6, 2024

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: June 24, 2020
• First Posted (Actual): June 25, 2020

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; docetaxel; pyrotinib; HER2 Exon 20 Mutation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; pyrotinib
• Other Study ID Numbers: HR-BLTN-III-NSCLC

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: Yes
• Studies a U.S. FDA-regulated device product: No