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
- Conditions
- HER2 Exon 20 MutationNon-squamous NSCLC
- Interventions
- Registration Number
- NCT04447118
- Lead Sponsor
- 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.
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 151
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Study treatment Arm Pyrotinib Pyrotinib maleate tablet, 400 mg, once daily (QD) Control Arm Docetaxel Docetaxel injection, 75 mg/m2, once every 3 weeks (Q3W)
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) 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
Name Time Method Overall survival (OS) 36 months Time from the date of randomization to death for any cause.
Progression-free survival 2(PFS2) 36 months Assessed by investigator according to the RECIST v1.1, or death for any cause, whichever comes first.
Patient reported outcome (PRO) using EORTC QLQ-C30 26 months Symptoms related to NSCLC,
Duration of response (DoR) 26 months Assessed by BIRC and investigator according to the RECIST v1.1.
Time to tumor progression (TTP) 26 months Assessed by BIRC and investigator according to the RECIST v1.1.
Objective response rate (ORR) 26 months Assessed by BIRC and investigator according to the RECIST v1.1.
Plasma concentrations of pyrotinib 26 months Pharmacokinetics (PK) of pyrotinib
AEs and SAEs 26 months Judged in accordance with NCI-CTCAE v5.0
Disease control rate (DCR) 26 months Assessed by BIRC and investigator according to the RECIST v1.1.
Patient reported outcomes (PRO) using the QLQ-LC13 26 months Symptoms related to NSCLC
Trial Locations
- Locations (102)
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Antwerp University Hospital (UZA)
🇧🇪Edegem, Belgium
University Hospital Gent
🇧🇪Gent, Belgium
Arkhangelsk Clinical Oncological Dispensary
🇷🇺Arkhangelsk, Russian Federation
Clinical hospital RZD-Medicine of St. Petersburg
🇷🇺Saint Petersburg, Russian Federation
Eurocityclinic LLC
🇷🇺Saint Petersburg, Russian Federation
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Harbin Medical University Cancer Hospital
🇨🇳Ha'erbin, Heilongjiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
The Second Affiliated of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Ankara Sehir Hastanesi
🇹🇷Ankara, Turkey
University of Kansas Medical Center (KUMC)
🇺🇸Kansas City, Kansas, United States
University of California - Irvine Medical Center
🇺🇸Orange, California, United States
Florida Cancer Specialists South Divisio
🇺🇸Fort Myers, Florida, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Florida Cancer Specialists North Divisio
🇺🇸Saint Petersburg, Florida, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Summit Cancer Centers - North Spokane
🇺🇸Spokane, Washington, United States
Royal North Shore Hospital
🇦🇺St Leonards, Saint Leonards, Australia
Calvary North Adelaide Hospital
🇦🇺North Adelaide, Australia
Border Medical Oncology
🇦🇺Albury, Australia
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
University Hospital (UZ) Leuven
🇧🇪Leuven, Belgium
beijing chest hospital,Capital medical university
🇨🇳Beijing, Beijing, China
the Second Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
The second affiliated hospital of ChongQing medical university
🇨🇳Chongqing, Chongqing, China
Peking university Cancer Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Guangdong Pharmaceutical University
🇨🇳Guangzhou, Guangdong, China
Cangzhou Hospital of Integrated Tcm-Wm.Hebei
🇨🇳Cangzhou, Hebei, China
First Affiliated Hospital of ZhengzhouUniversity
🇨🇳Zhengzhou, Henan, China
Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University
🇨🇳Changsha, Hunan, China
Hubei cancer hospital WardII
🇨🇳Wuhan, Hubei, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
Subei People's Hospital of Jiangsu Province
🇨🇳Yangzhou, Jiangsu, China
The affiliated hospital of inner mongolia medical univerity
🇨🇳Hohhot, Neimenggu, China
Shanghai Pulmonary Hospital, Tongji University
🇨🇳Shanghai, Shanghai, China
Shandong Cancer Hospital Affiliated to Shandong University
🇨🇳Jinan, Shandong, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Shanghai Chest Hospital
🇨🇳Shanghai, Shanghai, China
Fudan University Cancer hospital
🇨🇳Shanghai, Shanghai, China
Shanxi Provincial Cancer Hospital
🇨🇳Taiyuan, Shanxi, China
West China Hospital,Sichuan University
🇨🇳Chengdu, Sichuan, China
Yunnan Provincial Cancer Hospital
🇨🇳Kunming, Yunnan, China
SiChuan Cancer Hospital
🇨🇳Chengdu, Sichuan, China
The Second People's Hosipital of Yibin
🇨🇳Yibin, Sichuan, China
General Hospital of Tianjin Medical University
🇨🇳Tianjin, Tianjin, China
Hopital Bichat - Claude Bernard - AP-HP
🇫🇷Paris, France
The First Affiliated Hospital，ZheJiang University
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital ZheJiang University School Of Medicine
🇨🇳Hangzhou, Zhejiang, China
Centre Francois Baclesse
🇫🇷CAEN cedex 05, France
Centre Hospitalier Intercommunal Creteil
🇫🇷Creteil, France
ZheJiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
AP-HM - Hôpital Nord
🇫🇷Marseille cedex 20, France
Taizhou Hospital of Zhejiang Province
🇨🇳Taizhou, Zhejiang, China
CHRU Strasbourg
🇫🇷Strasbourg Cedex, France
Universitaetsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
CHU Toulouse - Hopital Larrey
🇫🇷Toulouse, France
Uniklinikum Giessen und Marburg
🇩🇪Giessen, Germany
Klinikverbund Kempten-Oberallgäu gGmbH
🇩🇪Kempten, Germany
POIS Leipzig GbR
🇩🇪Leipzig, Germany
Pius-Hospital Oldenburg, Centre of Radiotherapy and Medical Oncology, Dept. Medical Oncology
🇩🇪Oldenburg, Germany
Centro Riferimento Oncologico - Aviano
🇮🇹Aviano, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
ASST dei Sette Laghi-Ospedale di Circolo e Fondazione Macchi di Varese
🇮🇹Varese, Italy
Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico
🇮🇹Catania, Italy
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
🇮🇹Meldola (fc), Italy
Ajou University Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seoul, Bundang, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Centrum Onkologii KOMED
🇵🇱Konin, Poland
Salve-Medica
🇵🇱Lodz, Poland
Instytut Genetyki i Immunologii GENIM
🇵🇱Lublin, Poland
Med Polonia Sp. z o.o.
🇵🇱Poznan, Poland
Petrov National Medical Research Center of Oncology
🇷🇺St. Petersburg, Saint Petersburg, Russian Federation
JSC Group of companies Medsi
🇷🇺Moscow, Russian Federation
Hospital Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
🇷🇺Saint Petersburg, Russian Federation
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hospital Germans Trias i Pujol
🇪🇸Barcelona, Badalona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Badalona, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Spain
China Medical University Hospital
🇨🇳Taichung, Taiwan
Linkou Chang Gung Memorial Hospital (CGMHLK)
🇨🇳Taoyuan City, Taiwan
Baskent University Adana Application and Research Center
🇹🇷Adana, Turkey
Gulhane Training and Research Hospital
🇹🇷Keçiören, Turkey
Izmir Medical Park Hospital
🇹🇷Izmir, Turkey
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Trakya University Medical Faculty
🇹🇷Merkez, Turkey
Necmettin Erbakan University Selcuklu Faculty of Medicine
🇹🇷Konya, Turkey
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St. Mary's Hospital, The Catholic University of Korea
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
University of California (UC) Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States