PYRAMID-1: 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

Sponsor

Jiangsu HengRui Medicine Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04447118

Collaborator

(none)

150

Enrollment

103

Locations

Arms

37.6

Anticipated Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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).

Study Design

Study Type:

Interventional

Anticipated 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 :

Sep 11, 2020

Anticipated Primary Completion Date :

Oct 31, 2022

Anticipated Study Completion Date :

Oct 31, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Overall survival (OS) [36 months]
Time from the date of randomization to death for any cause.
Objective response rate (ORR) [26 months]
Assessed by BIRC and investigator according to the RECIST v1.1.
Disease control rate (DCR) [26 months]
Assessed by BIRC and investigator according to the RECIST v1.1.
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.
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,
Patient reported outcomes (PRO) using the QLQ-LC13 [26 months]
Symptoms related to NSCLC
Plasma concentrations of pyrotinib [26 months]
Pharmacokinetics (PK) of pyrotinib
AEs and SAEs [26 months]
Judged in accordance with NCI-CTCAE v5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California - Irvine Medical Center	Orange	California	United States	92868
2	University of California (UC) Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
3	Innovative Clinical Research Institute	Whittier	California	United States	33756
4	Florida Cancer Specialists South Divisio	Fort Myers	Florida	United States	33901
5	Florida Cancer Specialists North Divisio	Saint Petersburg	Florida	United States	33701
6	University of Kansas Medical Center (KUMC)	Kansas City	Kansas	United States	66160
7	David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
8	Gabrail Cancer Center	Canton	Ohio	United States	44718
9	Tennessee Oncology	Nashville	Tennessee	United States	33756
10	MD Anderson Cancer Center	Houston	Texas	United States	77030
11	Summit Cancer Centers - North Spokane	Spokane	Washington	United States	99208
12	Royal North Shore Hospital	St Leonards	Saint Leonards	Australia
13	Border Medical Oncology	Albury		Australia
14	St Vincent's Hospital Melbourne	Fitzroy		Australia
15	Sir Charles Gairdner Hospital	Nedlands		Australia
16	Calvary North Adelaide Hospital	North Adelaide		Australia
17	Antwerp University Hospital (UZA)	Edegem		Belgium
18	University Hospital Gent	Gent		Belgium
19	University Hospital (UZ) Leuven	Leuven		Belgium
20	the Second Affiliated Hospital of Anhui Medical University	Hefei	Anhui	China
21	beijing chest hospital,Capital medical university	Beijing	Beijing	China
22	Peking university Cancer Hospital	Beijing	Beijing	China
23	Peking university Cancer Hospital	Beijing	Beijing	China
24	The second affiliated hospital of ChongQing medical university	Chongqing	Chongqing	China
25	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong	China
26	Cangzhou Hospital of Integrated Tcm-Wm.Hebei	Cangzhou	Hebei	China
27	Harbin Medical University Cancer Hospital	Ha'erbin	Heilongjiang	China
28	First Affiliated Hospital of ZhengzhouUniversity	Zhengzhou	Henan	China
29	Henan Cancer Hospital	Zhengzhou	Henan	China
30	Hubei cancer hospital WardII	Wuhan	Hubei	China
31	Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University	Changsha	Hunan	China
32	Jiangsu Cancer Hospital	Nanjing	Jiangsu	China
33	Subei People's Hospital of Jiangsu Province	Yangzhou	Jiangsu	China
34	The Second Affiliated of Nanchang University	Nanchang	Jiangxi	China
35	Jilin Cancer Hospital	Changchun	Jilin	China
36	The affiliated hospital of inner mongolia medical univerity	Hohhot	Neimenggu	China
37	Shandong Cancer Hospital Affiliated to Shandong University	Jinan	Shandong	China
38	Shanghai Pulmonary Hospital, Tongji University	Shanghai	Shanghai	China	200433
39	Fudan University Cancer hospital	Shanghai	Shanghai	China
40	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China
41	Shanghai Chest Hospital	Shanghai	Shanghai	China
42	Shanxi Provincial Cancer Hospital	Taiyuan	Shanxi	China
43	SiChuan Cancer Hospital	Chengdu	Sichuan	China
44	West China Hospital,Sichuan University	Chengdu	Sichuan	China
45	The Second People's Hosipital of Yibin	Yibin	Sichuan	China
46	General Hospital of Tianjin Medical University	Tianjin	Tianjin	China
47	Yunnan Provincial Cancer Hospital	Kunming	Yunnan	China
48	Sir Run Run Shaw Hospital ZheJiang University School Of Medicine	Hangzhou	Zhejiang	China
49	The First Affiliated Hospital，ZheJiang University	Hangzhou	Zhejiang	China
50	ZheJiang Cancer Hospital	Hangzhou	Zhejiang	China
51	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang	China
52	Centre Francois Baclesse	CAEN cedex 05		France
53	Centre Hospitalier Intercommunal Creteil	Creteil		France
54	AP-HM - Hôpital Nord	Marseille cedex 20		France
55	Hopital Bichat - Claude Bernard - AP-HP	Paris		France
56	CHRU Strasbourg	Strasbourg Cedex		France
57	CHU Toulouse - Hopital Larrey	Toulouse		France
58	Universitaetsklinikum Carl Gustav Carus Dresden	Dresden		Germany
59	Uniklinikum Giessen und Marburg	Giessen		Germany
60	Klinikverbund Kempten-Oberallgäu gGmbH	Kempten		Germany
61	POIS Leipzig GbR	Leipzig		Germany
62	Pius-Hospital Oldenburg, Centre of Radiotherapy and Medical Oncology, Dept. Medical Oncology	Oldenburg		Germany
63	Centro Riferimento Oncologico - Aviano	Aviano		Italy
64	Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico	Catania		Italy
65	Istituto Romagnolo per lo Studio dei Tumori Dino Amadori	Meldola (fc)		Italy
66	Istituto Europeo di Oncologia	Milano		Italy
67	ASST dei Sette Laghi-Ospedale di Circolo e Fondazione Macchi di Varese	Varese		Italy
68	Seoul National University Bundang Hospital	Seoul	Bundang	Korea, Republic of
69	Ajou University Hospital	Gyeonggi-do		Korea, Republic of
70	Asan Medical Center	Seoul		Korea, Republic of
71	Korea University Anam Hospital	Seoul		Korea, Republic of
72	Samsung Medical Center	Seoul		Korea, Republic of
73	Seoul St. Mary's Hospital, The Catholic University of Korea	Seoul		Korea, Republic of
74	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of
75	Centrum Onkologii KOMED	Konin		Poland
76	Salve-Medica	Lodz		Poland
77	Instytut Genetyki i Immunologii GENIM	Lublin		Poland
78	Med Polonia Sp. z o.o.	Poznan		Poland
79	Petrov National Medical Research Center of Oncology	St. Petersburg	Saint Petersburg	Russian Federation
80	Arkhangelsk Clinical Oncological Dispensary	Arkhangelsk		Russian Federation
81	JSC Group of companies Medsi	Moscow		Russian Federation
82	Clinical hospital RZD-Medicine of St. Petersburg	Saint Petersburg		Russian Federation
83	Eurocityclinic LLC	Saint Petersburg		Russian Federation
84	Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)	Saint Petersburg		Russian Federation
85	Hospital Germans Trias i Pujol	Barcelona	Badalona	Spain
86	Hospital Universitario Vall d'Hebron	Barcelona	Badalona	Spain
87	Hospital Clinic Barcelona	Barcelona		Spain
88	Hospital Fundación Jiménez Díaz	Madrid		Spain
89	Hospital Universitario 12 de Octubre	Madrid		Spain
90	Hospital Regional Universitario de Malaga	Malaga		Spain
91	Complejo Hospitalario de Navarra	Pamplona		Spain
92	Hospital Universitario Virgen del Rocio	Sevilla		Spain
93	Instituto Valenciano de Oncologia	Valencia		Spain
94	China Medical University Hospital	Taichung		Taiwan
95	Taipei Veterans General Hospital	Taipei		Taiwan
96	Linkou Chang Gung Memorial Hospital (CGMHLK)	Taoyuan City		Taiwan
97	Baskent University Adana Application and Research Center	Adana		Turkey
98	Ankara Sehir Hastanesi	Ankara		Turkey
99	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey
100	Izmir Medical Park Hospital	Izmir		Turkey
101	Gulhane Training and Research Hospital	Keçiören		Turkey
102	Necmettin Erbakan University Selcuklu Faculty of Medicine	Konya		Turkey
103	Trakya University Medical Faculty	Merkez		Turkey