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

Non-squamous NSCLC Clinical Trial

— PYRAMID-1  

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04447118
• Other study ID #: HR-BLTN-III-NSCLC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 11, 2020
• Est. completion date: October 31, 2023

Study information

• Verified date: March 2023
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 151
• Est. completion date: October 31, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• HER2 Exon 20 Mutation
• Non-squamous NSCLC

Intervention

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.
• Docetaxel
75 mg/m2, once every 3 weeks (Q3W), will be administered by intravenous infusion over 1 hour, with 21 days as a cycle.

Locations

Country	Name	City	State
Australia	Border Medical Oncology	Albury
Australia	St Vincent's Hospital Melbourne	Fitzroy
Australia	Sir Charles Gairdner Hospital	Nedlands
Australia	Calvary North Adelaide Hospital	North Adelaide
Australia	Royal North Shore Hospital	St Leonards	Saint Leonards
Belgium	Antwerp University Hospital (UZA)	Edegem
Belgium	University Hospital Gent	Gent
Belgium	University Hospital (UZ) Leuven	Leuven
China	beijing chest hospital,Capital medical university	Beijing	Beijing
China	Peking university Cancer Hospital	Beijing	Beijing
China	Cangzhou Hospital of Integrated Tcm-Wm.Hebei	Cangzhou	Hebei
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University	Changsha	Hunan
China	SiChuan Cancer Hospital	Chengdu	Sichuan
China	West China Hospital,Sichuan University	Chengdu	Sichuan
China	The second affiliated hospital of ChongQing medical university	Chongqing	Chongqing
China	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong
China	Harbin Medical University Cancer Hospital	Ha'erbin	Heilongjiang
China	Sir Run Run Shaw Hospital ZheJiang University School Of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital,ZheJiang University	Hangzhou	Zhejiang
China	ZheJiang Cancer Hospital	Hangzhou	Zhejiang
China	the Second Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The affiliated hospital of inner mongolia medical univerity	Hohhot	Neimenggu
China	Shandong Cancer Hospital Affiliated to Shandong University	Jinan	Shandong
China	Yunnan Provincial Cancer Hospital	Kunming	Yunnan
China	The Second Affiliated of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Fudan University Cancer hospital	Shanghai	Shanghai
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Shanghai Chest Hospital	Shanghai	Shanghai
China	Shanghai Pulmonary Hospital, Tongji University	Shanghai	Shanghai
China	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi
China	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang
China	General Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Hubei cancer hospital WardII	Wuhan	Hubei
China	Subei People's Hospital of Jiangsu Province	Yangzhou	Jiangsu
China	The Second People's Hosipital of Yibin	Yibin	Sichuan
China	First Affiliated Hospital of ZhengzhouUniversity	Zhengzhou	Henan
China	Henan Cancer Hospital	Zhengzhou	Henan
France	Centre Francois Baclesse	CAEN cedex 05
France	Centre Hospitalier Intercommunal Creteil	Creteil
France	AP-HM - Hôpital Nord	Marseille cedex 20
France	Hopital Bichat - Claude Bernard - AP-HP	Paris
France	CHRU Strasbourg	Strasbourg Cedex
France	CHU Toulouse - Hopital Larrey	Toulouse
Germany	Universitaetsklinikum Carl Gustav Carus Dresden	Dresden
Germany	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
Italy	Centro Riferimento Oncologico - Aviano	Aviano
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	Istituto Europeo di Oncologia	Milano
Italy	ASST dei Sette Laghi-Ospedale di Circolo e Fondazione Macchi di Varese	Varese
Korea, Republic of	Ajou University Hospital	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Bundang Hospital	Seoul	Bundang
Korea, Republic of	Seoul St. Mary's Hospital, The Catholic University of Korea	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Poland	Centrum Onkologii KOMED	Konin
Poland	Salve-Medica	Lodz
Poland	Instytut Genetyki i Immunologii GENIM	Lublin
Poland	Med Polonia Sp. z o.o.	Poznan
Russian Federation	Arkhangelsk Clinical Oncological Dispensary	Arkhangelsk
Russian Federation	JSC Group of companies Medsi	Moscow
Russian Federation	Clinical hospital RZD-Medicine of St. Petersburg	Saint Petersburg
Russian Federation	Eurocityclinic LLC	Saint Petersburg
Russian Federation	Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)	Saint Petersburg
Russian Federation	Petrov National Medical Research Center of Oncology	St. Petersburg	Saint Petersburg
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital Germans Trias i Pujol	Barcelona	Badalona
Spain	Hospital Universitario Vall d'Hebron	Barcelona	Badalona
Spain	Hospital Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Instituto Valenciano de Oncologia	Valencia
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital (CGMHLK)	Taoyuan City
Turkey	Baskent University Adana Application and Research Center	Adana
Turkey	Ankara Sehir Hastanesi	Ankara
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Izmir Medical Park Hospital	Izmir
Turkey	Gulhane Training and Research Hospital	Keçiören
Turkey	Necmettin Erbakan University Selcuklu Faculty of Medicine	Konya
Turkey	Trakya University Medical Faculty	Merkez
United States	Gabrail Cancer Center	Canton	Ohio
United States	Florida Cancer Specialists South Divisio	Fort Myers	Florida
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Kansas Medical Center (KUMC)	Kansas City	Kansas
United States	Tennessee Oncology	Nashville	Tennessee
United States	David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of California - Irvine Medical Center	Orange	California
United States	University of California (UC) Davis Comprehensive Cancer Center	Sacramento	California
United States	Florida Cancer Specialists North Divisio	Saint Petersburg	Florida
United States	Summit Cancer Centers - North Spokane	Spokane	Washington
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  China,  France,  Germany,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey, 

Outcome

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