A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions

Carcinoma, Non-Small-Cell Lung Clinical Trial

— PAPILLON  

Official title:

A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04538664
• Other study ID #: CR108850
• Secondary ID: 2020-000633-4061
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 13, 2020
• Est. completion date: January 31, 2026

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy, as demonstrated by progression-free survival (PFS), in participants treated with amivantamab in combination with chemotherapy, versus chemotherapy alone in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by EGFR Exon 20ins mutations.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 308
• Est. completion date: January 31, 2026
• Est. primary completion date: May 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant must have histologically or cytologically confirmed, locally advanced or metastatic, nonsquamous non-small cell lung cancer (NSCLC) with documented primary epidermal growth factor receptor (EGFR) Exon 20ins activating mutation
• Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Participant must agree to genetic characterization of tumor status through the required pretreatment tumor biopsy (or submission of equivalent archival material), as well as baseline and periodic blood samples for analysis of tumor mutations in the bloodstream
• A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study

Exclusion Criteria:

• Participant has evidence of synchronous NSCLC disease (as suggested by genetic characterization or radiographic appearance)
• Participant has untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to randomization is eligible)
• Participant has history of spinal cord compression that has not been treated definitively with surgery or radiation
• Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD, or radiation pneumonitis
• Participant has a contraindication to the use of carboplatin or pemetrexed (refer to local prescribing information for each agent). Participant has a history of hypersensitivity to, or cannot take, vitamin B12 or folic acid

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Amivantamab
Amivantamab will be administered as an IV infusion at a dose of 1400 mg (1750 mg if body weight is >=80 kilogram [kg]) by once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is >=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3 and will continue the same treatment in OLE phase then in LTE phase.
• Pemetrexed
Pemetrexed will be administered as 500 mg/m^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and then as maintenance monotherapy until disease progression in Arm A and will continue the same treatment in OLE phase then in LTE phase.
• Carboplatin
Carboplatin will be administered as AUC 5 IV infusion for up to 4 cycles on Day 1 of each 21-day cycle.
• Pemetrexed
Pemetrexed will be administered as 500 mg/m^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and then as maintenance monotherapy until disease progression in Arm B and will continue the same treatment in OLE phase then in LTE phase.

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown
Australia	St George Hospital	Kogarah
Australia	Cabrini Medical Centre	Malvern
Australia	Sir Charles Gairdner Hospital	Nedlands
Belgium	UZ Leuven	Leuven
Belgium	Algemeen Ziekenhuis Delta	Roeselare
Belgium	CHU UCL Namur - Site Godinne	Yvoir
Brazil	Fundacao Pio XII	Barretos
Brazil	Cetus Oncologia	Belo Horizonte
Brazil	Ynova Pesquisa Clinica	Florianopolis
Brazil	Oncosite - Centro de Pesquisa Clínica em Oncologia Ltda	Ijui
Brazil	Liga Norte Riograndense Contra O Cancer	Natal
Brazil	UPCO Unidade de Pesquisa Clinica em Oncologia	Pelotas
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS	Porto Alegre
Brazil	Instituto D Or de Pesquisa e Ensino (IDOR)	Rio de Janeiro
Brazil	Ministerio da Saude - Instituto Nacional do Cancer	Rio De Janeiro
Brazil	Oncoclinicas Rio de Janeiro S A	Rio de Janeiro
Brazil	Fundacao Antonio Prudente A C Camargo Cancer Center	Sao Paulo
Brazil	Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo	Sao Paulo
Brazil	Núcleo de Pesquisa São Camilo	Sao Paulo
Brazil	IOS - Instituto de Oncologia de Sorocaba Dr. Gilson Delgado	Sorocaba
Brazil	Hospital Evangélico de Cachoeiro de Itapemirim	Vitoria
Canada	McGill University Health Centre	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
China	Beijing Cancer Hospital	Beijing
China	Beijing Chest hospital, Capital medical university	Beijing
China	Chinese PLA General Hospital	Beijing
China	Peking University International Hospital	Beijing
China	Jilin cancer hospital	Changchun
China	Hunan Cancer hospital	Changsha
China	The First People's Hospital Of Changzhou	Changzhou
China	West China Hospital Sichuan University	Chengdu
China	Chongqing University Cancer Hospital	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou
China	The First Affiliated Hospital Sun Yat sen University	Guang Zhou
China	Zhejiang Cancer Hospital	Hang Zhou
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	The First Affiliated Hospital Zhejiang University College of Medicine	Hangzhou
China	The Second Affiliated Hospital of Zhejiang University College of Medicine	Hangzhou
China	Harbin medical university cancer hospital	Harbin
China	Taizhou Hospital of Zhejiang Province	Linhai
China	Nanjing Drum Tower Hospital	Nanjing
China	Fudan University Shanghai Cancer Center	Shanghai
China	Shanghai Chest Hospital	Shanghai
China	Shanghai East Hospital	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai
China	Shengjing Hospital Of China Medical University	Shenyang
China	Cancer hospital Chinese Academy of Medical Sciences, Shenzhen Center	Shenzhen
China	Tianjin Medical University General Hospital	Tianjin
China	Weifang People's Hospital	Weifang
China	TongJi Hospital of TongJi Medical College of Huazhong University of Science & Technology	Wuhan
China	Hospital of Jiangnan University	Wuxi
China	The First Affiliated Hospital of Xian Jiaotong University	XI An
China	Yantai Yuhuangding Hospital	Yantai
China	Henan Cancer Hospital	Zhengzhou
France	Institut Bergonie	Bordeaux
France	Hospices Civils de Lyon HCL	Bron
France	Centre Georges François Leclerc	Dijon
France	Centre Hospitalier Le Mans	le mans Cedex 9
France	CHR Hôpital Calmette	Lille CEDEX
France	CHU Nantes - Hopital Nord Laënnec	NANTES cedex 1
France	Institut Curie	Paris
France	CHU Bordeaux	Pessac
France	HIA Begin	Saint Mande
Germany	Zentralklinik Bad Berka GmbH	Bad Berka
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	Asklepios Klinik Gauting GmbH - Asklepios Fachkliniken Munchen-Gauting	Gauting
Germany	Thoraxklinik am Universitatsklinikum Heidelberg	Heidelberg
Germany	Onkologische Schwerpunktpraxis	Heilbronn
Germany	Kliniken der Stadt Koeln gGmbH	Koeln
Germany	Universitaetsklinikum Koeln	Koeln
Germany	Bethanien Krankenhaus	Moers
Germany	Pius-Hospital Oldenburg	Oldenburg
Germany	Oncologianova GmbH	Recklinghausen
Hungary	Orszagos Koranyi Tbc es Pulmonologiai Intezet	Budapest
Hungary	Mátrai Gyógyintézet-Bronchológia	Gyöngyös
Hungary	Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz	Szekesfehervar
Hungary	Markusovszky Egyetemi Oktatokorhaz	Szombathely
Hungary	Tudogyogyintezet Torokbalint	Torokbalint
India	Basavatarakam Indo-American Hospital	Hyderabad
India	Tata Medical Center	Kolkata
India	Tata Memorial Hospital	Mumbai
India	HCG Manavta Cancer Centre	Nasik
India	Rajiv Gandhi Cancer Institute & Research Centre	New Delhi
India	Noble Hospital Pvt Ltd	Pune
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah Tikva
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv
Italy	A O U Sant Orsola Malpighi	Bologna
Italy	Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico	Catania
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	San Gerardo Hospital	Monza
Italy	Ospedale S. Maria Delle Croci	Ravenna
Italy	Irccs Gemelli	Roma
Italy	Istituto Clinico Humanitas	Rozzano
Japan	Juntendo University Hospital	Bunkyo Ku
Japan	Saitama Medical University International Medical Center	Hidaka
Japan	National Hospital Organization Himeji Medical Center	Himeji
Japan	Kansai Medical University Hospital	Hirakata
Japan	Kanazawa University Hospital	Kanazawa
Japan	National Cancer Center Hospital East	Kashiwa
Japan	Kishiwada City Hospital	Kishiwada
Japan	Kobe City Medical Center General Hospital	Kobe
Japan	Kurashiki Central Hospital	Kurashiki
Japan	Kurume University Hospital	Kurume
Japan	Matsusaka Municipal Hospital	Matsusaka
Japan	Aichi Cancer Center Hospital	Nagoya Shi
Japan	National Hospital Organization Nagoya Medical Center	Nagoya-shi
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Kindai University Hospital	Osaka Sayama shi
Japan	Kitasato University Hospital	Sagamihara
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	Iwate Medical University Hospital	Shiwa-gun
Japan	Shizuoka Cancer Center	Shizuoka
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Ehime University Hospital	Toon-shi
Japan	Wakayama Medical University Hospital	Wakayama
Japan	National Hospital Organization Yamaguchi Ube Medical Center	Yamaguchi
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	GyeongSang National University Hospital	Gyeongsangnam-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St Mary s Hospital	Seoul
Malaysia	Hospital Pulau Pinang	George Town
Malaysia	Hospital Sultan Ismail	Johor Bahru
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Mexico	Centro Oncológico de Chihuahua	Chihuahua
Mexico	Instituto Nacional de Cancerologia	Ciudad de Mexico
Mexico	Médica Sur	Ciudad de Mexico
Mexico	Mexico Centre for Clinical Research, S.A. de C.V.	Ciudad de Mexico
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara
Mexico	Health Pharma Professional Research	Mexico
Mexico	i Can Oncology Center	Monterrey
Mexico	Oncologia Integral Satelite	Naucalpan
Poland	Centrum Onkologii im. Prof. F. Lukaszczyka	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Szpitale Pomorskie Sp z o o	Gdynia
Poland	Warminsko-Mazurskie Centrum Chorob Pluc w Olsztynie	Olsztyn
Poland	Private Specialist Hospitals - MedPolonia	Poznan
Poland	Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy	Warszawa
Portugal	Chlc - Hosp. Sto Antonio Dos Capuchos	Lisboa
Portugal	Hosp. Cuf Descobertas	Lisboa
Portugal	Centro Hospitalar Universitario do Porto, EPE	Porto
Portugal	Instituto Portugues de Oncologia	Porto
Portugal	Centro Hospitalar de Vila Nova de Gaia Espinho E P E	Vila Nova de Gaia
Puerto Rico	Pan American Center for Oncology Trials LLC	Rio Piedras
Russian Federation	Irkutsk Regional Oncology Dispensary	Irkutsk
Russian Federation	Moscow City Oncology Hospital ? 62	Krasnogorsk
Russian Federation	Krasnoyarsk Regional Oncology Dispensary	Krasnoyarsk
Russian Federation	Leningrad Regional Oncology Dispensary	Kuzmolovsky
Russian Federation	MCK	Moscow
Russian Federation	City Clinical Hospital #1	Nalchik
Russian Federation	Nizhny Novgorod Regional Oncological Dispensary	Nizhniy Novgorod
Russian Federation	N.N. Petrov Research Institute Of Oncology	Saint Petersburg
Russian Federation	Leningrad Regional Clinical Hospital	Saint-Petersburg
Russian Federation	Oncology Medical Clinics AV Medical group	St-Petersburg
Russian Federation	Tomsk Cancer Research Institute	Tomsk
Russian Federation	Bashkir State Medical University	Ufa
Russian Federation	Yaroslavl Regional Clinical Oncology Hospital	Yaroslavl
Spain	Hosp. Univ. A Coruna	A Coruna
Spain	Inst. Cat. D'Oncologia-Badalona	Badalona
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Univ. Quiron Dexeus	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. de Burgos	Burgos
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. Univ. Pta. de Hierro Majadahonda	Majadahonda
Spain	Hosp. Virgen de La Victoria	Málaga
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp. Virgen Del Rocio	Seville
Spain	Hosp. Clinico Univ. Lozano Blesa	Zaragoza
Taiwan	Chang Gung Medical Foundation	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taipei Medical University Shuang Ho Hospital	New Taipei
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei City
Thailand	Phramongkutklao Hospital and Medical College	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Songklanagarind Hospital, Prince of Songkla University	Songkla
Turkey	Adana City Hospital	Adana
Turkey	Baskent University Medical Faculty Adana Application and Research Center	Adana
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Gazi University Hospital	Ankara
Turkey	Trakya University Medical Faculty	Edirne
Turkey	Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi	Istanbul
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi Ic Hastaliklari Anabilim Dali Medikal Onkoloji Bd	Istanbul
Turkey	Medipol Mega University Hospital	Istanbul
Turkey	Izmir Medical Park Hospital	Izmir
Ukraine	Dnipropetrovsk State Medical Academy, Dnipropetrovsk City Multifield Clinical Hospital # 4	Dnipro
Ukraine	Medical Center 'Ok Clinic' of LLC 'International Institute of Clinical Studies'	Kyiv
Ukraine	National Cancer Institute	Kyiv
United Kingdom	Edinburgh Cancer Centre Western General	Edinburgh
United Kingdom	The Royal Marsden NHS Trust	London
United Kingdom	The Royal Marsden NHS Trust	Sutton
United States	University Cancer And Blood Center LLC	Athens	Georgia
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Regional Cancer Care Associates LLC	East Brunswick	New Jersey
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Columbia University Medical Center	New York	New York
United States	Langone Health at NYC University, NYU School of Medicine	New York	New York
United States	University of California Irvine	Orange	California
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University Medical Center	Saint Louis	Missouri
United States	Blue Ridge Cancer Care	Salem	Virginia
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	UCLA	Santa Monica	California
United States	Sanford Health	Sioux Falls	South Dakota
United States	H. Lee Moffitt Cancer & Research Institute	Tampa	Florida
United States	Texas Oncology Pa	Tyler	Texas
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)	PFS was defined as the time from randomization until the date of objective disease progression based on BICR using RECIST version 1.1 or death (by any cause) in the absence of progression, whichever came first. Participants who have not progressed or have not died at the time of analysis were censored at the time of the latest date of their last evaluable RECIST version 1.1 assessment. Pharmacodynamic: Sum of diameters increased by greater than or equal to (>=)20 percent (%) and >=5 millimeter (mm) from nadir (including baseline if it was smallest sum).	From randomization to either disease progression or death whichever occurs first (up to 29 months)
Secondary	Objective Response Rate (ORR)		Up to 5 years 3 months
Secondary	Duration of Response (DoR)		Up to 5 years 3 months
Secondary	Overall Survival (OS)		Up to 5 years 3 months
Secondary	Time to Subsequent Therapy (TST)		Up to 5 years 3 months
Secondary	Progression-Free Survival After First Subsequent Therapy (PFS2)		Up to 5 years 3 months
Secondary	Time to Symptomatic Progression (TTSP)		Up to 5 years 3 months
Secondary	Number of Participants Treatment-emergent Adverse Events (TEAEs)		From Day 1 to 5 years 2 months
Secondary	Number of Participants TEAEs With Severity		From Day 1 to 5 years 2 months
Secondary	Number of Participants With Clinical Laboratory Abnormalities		Up to 5 years 3 months
Secondary	Number of Participants With Vital Signs Abnormalities		Up to 5 years 3 months
Secondary	Number of Participants With Physical Examination Abnormalities		Up to 5 years 3 months
Secondary	Serum Concentration of Amivantamab		Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1)
Secondary	Number of Participants With Anti-Amivantamab Antibodies		Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1)
Secondary	Change From Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)		From baseline to 5 years 3 months
Secondary	Change From Baseline in Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF)		From baseline to 5 years 3 months