A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer

Advanced or Metastatic Non-small Cell Lung Cancer Clinical Trial

— PALOMA-3  

Official title:

A Phase 3, Open-label, Randomized Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Patients With EGFR-mutated Advanced or Metastatic Non-small Cell Lung Cancer After Progression on Osimertinib and Chemotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05388669
• Other study ID #: CR109211
• Secondary ID: 2022-000525-2561
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 5, 2022
• Est. completion date: January 9, 2025

Study information

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

Clinical Trial Summary

The purpose of the study is to simplify amivantamab intravenous administration and to reduce dose times, by assessing a new formulation of amivantamab, amivantamab subcutaneous and co-formulated with recombinant human hyaluronidase (SC-CF), for subcutaneous administration. This formulation has the potential to enhance both the patient and physician experience with amivantamab by providing easier and accelerated administration.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 418
• Est. completion date: January 9, 2025
• Est. primary completion date: January 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have histologically or cytologically confirmed, advanced or metastatic non-small cell lung cancer (NSCLC), characterized by either epidermal growth factor receptor (EGFR) Exon 19 deletion (Exon 19del) or Exon 21 leucine 858 to arginine substitution (Exon 21 L858R) mutation by an Food and Drug Administration (FDA)-approved or other validated test of either circulating tumor deoxyribonucleic acid (ctDNA) or tumor tissue in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United Started [US]) or an accredited local laboratory (sites outside of the US)

• Have progressed on or after osimertinib (or another approved 3rd generation epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKI]) and platinum-based chemotherapy (irrespective of order). a) The 3rd generation EGFR TKI must have been administered as the first EGFR TKI for metastatic disease or as the second TKI after prior treatment with first- or second-generation EGFR TKI in participants with metastatic EGFR T790M mutation positive NSCLC. b) Participants who decline or are otherwise ineligible for chemotherapy may be enrolled after discussion with the medical monitor. c) Any adjuvant or neoadjuvant treatment, whether with a 3rd generation EGFR TKI or platinum based chemotherapy, would count towards the prior treatment requirement if the participant experienced disease

• Have at least 1 measurable lesion, according to response evaluation criteria in solid tumors (RECIST) version 1.1

• Have an eastern cooperative oncology group (ECOG) performance status of 0 to 1

• Any toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade less than or equal to (<=) 2 peripheral neuropathy, and Grade <=2 hypothyroidism stable on hormone replacement)

Exclusion Criteria:

• Participant has received cytotoxic, investigational, or targeted therapies beyond one regimen of platinum-based chemotherapy and EGFR inhibitors

• Participant has received radiotherapy for palliative purposes less than 7 days prior to randomization

• Participant has symptomatic or progressive brain metastases

• Participant has leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation

• Participant has uncontrolled tumor-related pain

• Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis

Related Conditions & MeSH terms

• Advanced or Metastatic Non-small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• Lazertinib
Lazertinib tablets will be administered orally.
• Amivantamab Subcutaneous and Co-Formulated with Recombinant Human Hyaluronidase (SC CF)
Amivantamab injection will be administered subcutaneously by manual injection
• Amivantamab Intravenous
Amivantamab will be administered by IV infusion

Locations

Country	Name	City	State
Argentina	CEMIC (Centro de Educación Médica e Investigaciones Clínicas)	Buenos Aires
Argentina	IADT Instituto Argentino de Diagnostico y Tratamiento	Caba
Argentina	Centro Oncológico Korben	Ciudad Autonoma de Buenos Aires
Argentina	Cemaic - Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica	Cordoba
Argentina	Sanatorio Allende	Cordoba
Argentina	Clínica Viedma	Viedma
Australia	Cancer Research SA	Adelaide
Australia	Chris O'Brien Lifehouse	Camperdown
Australia	Peter MacCallum Cancer Centre	Melbourne
Australia	St John of God Hospital Murdoch	Murdoch
Australia	Westmead Hospital	Westmead
Australia	Princess Alexandra Hospital	Woolloongabba
Brazil	Fundacao Pio XII	Barretos
Brazil	Cetus Oncologia	Belo Horizonte
Brazil	Instituto Cionc de Ensino e Pesquisa S/S	Curitiba
Brazil	Ynova Pesquisa Clinica	Florianopolis
Brazil	Fundacao Sao Francisco Xavier HMC Unidade de Oncologia	Ipatinga
Brazil	UPCO Unidade de Pesquisa Clinica em Oncologia	Pelotas
Brazil	Uniao Brasileira de Educaçao e Assistencia-Hospital Sao Lucas da PUCRS	Porto Alegre
Brazil	Impar Servicos Hospitalares S/A	Rio de Janeiro
Brazil	Instituto D Or de Pesquisa e Ensino (IDOR)	Rio de Janeiro
Brazil	Oncoclinicas Rio de Janeiro S A	Rio de Janeiro
Brazil	Nucleo de Oncologia da Bahia	Salvador
Brazil	CEPHO - Centro de Estudos e Pesquisa de Hematologia e Oncologia	Santo Andre
Brazil	Impar Servicos Hospitalares SA - Hospital Nove de Julho	Sao Paulo
Brazil	Núcleo de Pesquisa São Camilo	São Paulo
Brazil	Onco Star SP Oncologia Ltda	São Paulo
Brazil	Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein	São Paulo
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
China	Beijing Chest hospital, Capital medical university	Beijing
China	Beijing Friendship Hospital Capital Medical University	Beijing
China	Beijing Shijitan Hospital, Capital Medical University	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing
China	Peking University Third Hospital	Beijing
China	Jilin cancer hospital	Changchun
China	The First People's Hospital Of Changzhou	Changzhou
China	Sichuan Cancer Hospital	Chengdu
China	West China Hospital Sichuan University	Chengdu
China	Chongqing University Cancer Hospital	Chongqing
China	Southwest Hospital	ChongQing
China	First Affiliated Hospital of Gannan Medical University	Ganzhou
China	The First Affiliated Hospital Sun Yat sen University	Guang Zhou
China	Sun Yat-Sen Memorial Hospital Sun Yat-sen University	Guangzhou
China	Zhejiang Cancer Hospital	Hang Zhou
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	The Second Affiliated Hospital of Zhejiang University College of Medicine	Hangzhou
China	Harbin medical university cancer hospital	Harbin
China	Huizhou First Hospital	Huizhou
China	Huizhou Municipal Central Hospital	Huizhou
China	Liuzhou people's Hospital	Liuzhou
China	Affiliated Hospital of North Sichuan Medical College	Nanchong
China	Fudan University Shanghai Cancer Center	Shanghai
China	Shenzhen People s Hospital	Shen Zhen Shi
China	Shengjing Hospital of China Medical University	Shenyang
China	Shenzhen university General Hospital	Shenzhen
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	Union Hospital Tongji Medical College of Huazhong University of Science and Technology	Wuhan
China	The First Affiliated Hospital of Xian Jiaotong University	XI An
China	Xiangyang Central Hospital	Xiangyang
China	Yantai Yuhuangding Hospital	Yantai
China	Henan Cancer Hospital	Zhengzhou
France	CHU Grenoble	La Tronche
France	Institute Coeur Poumon	Lille
France	CHU de Limoges Hopital Dupuytren	Limoges
France	Hopital Nord	Marseille Cedex 20
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	Niels-Stensen-Kliniken Franziskus-Hospital Harderberg	Georgsmarienhütte
Germany	Universitaetsklinikum Giessen und Marburg GmbH	Giessen
Germany	Munster University Hospital	Münster
Germany	Oncologianova GmbH	Recklinghausen
Germany	Onkologische Schwerpunktpraxis	Weinsberg
Israel	Rambam Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah-Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Italy	Oncologia Medica - Irccs - Istituto Tumori Giovanni Paolo II	Bari
Italy	A O U Sant Orsola Malpighi	Bologna
Italy	European Institute of Oncology	Milano
Italy	Aou San Luigi Gonzaga	Orbassano
Italy	Istituto Oncologico Veneto - IRCCS	Padova
Italy	Ospedale S. Maria Delle Croci	Ravenna
Italy	A.O. San Camillo Forlanini	Roma
Italy	Istituto Nazionale Tumori Regina Elena	Rome
Italy	Istituto Clinico Humanitas	Rozzano
Japan	National Cancer Center Hospital	Chuo Ku
Japan	National Hospital Organization Himeji Medical Center	Himeji
Japan	Kansai Medical University Hospital	Hirakata
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kurashiki Central Hospital	Kurashiki
Japan	Kurume University Hospital	Kurume
Japan	Matsusaka Municipal Hospital	Matsusaka
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Okayama University Hospital	Okayama
Japan	Osaka International Cancer Institute	Osaka
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	Shizuoka Cancer Center	Shizuoka
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Fujita Health University Hospital	Toyoake
Japan	National Hospital Organization Osaka Toneyama Medical Center	Toyonaka-shi
Japan	Wakayama Medical University Hospital	Wakayama
Japan	National Hospital Organization Iwakuni Clinical Center	Yamaguchi
Japan	National Hospital Organization Yamaguchi Ube Medical Center	Yamaguchi
Korea, Republic of	CHA Bundang Medical Center, CHA University	Gyeonggi-do
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	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Malaysia	Pantai Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	Prince Court Medical Centre	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Umum Sarawak	Kuching
Malaysia	Beacon Hospital Sdn Bhd	Petaling Jaya
Malaysia	Sunway Medical Centre	Petaling Jaya
Poland	Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy	Bydgoszcz
Poland	Krakowski Szpital Specjalityczny im. Jana Pawla II	Krakow
Poland	Mazowieckie Centrum Leczenia Chorob Pluc	Otwock
Poland	Private Specialist Hospitals - MedPolonia	Poznan
Poland	Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy	Warszawa
Portugal	Hospital de Braga	Braga
Portugal	Hosp. Cuf Descobertas	Lisboa
Portugal	Hospital da Luz, SA	Lisboa
Portugal	Hospital Pedro Hispano	Senhora da Hora,
Spain	Hosp. Univ. A Coruna	A Coruna
Spain	Hosp. Gral. Univ. de Alicante	Alicante
Spain	Hosp. Clinic de Barcelona	Barcelona
Spain	Hosp. Univ. Quiron Dexeus	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Reina Sofia	Córdoba
Spain	Hosp. Univ. Insular de Gran Canaria	Las Palmas de Gran Canaria
Spain	Hosp. Univ. Lucus Augusti	Lugo
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Pta. de Hierro Majadahonda	Majadahonda
Spain	Hosp. Regional Univ. de Malaga	Málaga
Spain	Hosp. Univ. Central de Asturias	Oviedo
Spain	Hosp. Univ. Son Espases	Palma de Mallorca
Spain	Hosp. Virgen Del Rocio	Sevilla
Spain	Hosp. Univ. I Politecni La Fe	Valencia
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Chang Kung Memorial Hospital	Kaohsiung City
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	National Taiwan University Cancer Center	Taipei City
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan
Thailand	Phramongkutklao Hospital and Medical College	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Chiang Mai University	Chiangmai
Turkey	Adana Baskent Hospital	Adana
Turkey	Adana City Hospital	Adana
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Gazi University Hospital	Ankara
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Trakya University Medical Faculty	Edirne
Turkey	Acibadem Maslak Hospital	Istanbul
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Dokuz Eylul University Medical Faculty	Izmir
Turkey	IEU Medical Point Hospital	Izmir
Turkey	Medical Park Samsun Hastanesi	Samsun
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Imperial College Healthcare	London
United Kingdom	Newcastle Freeman Hospital	Newcastle Upon Tyne
United Kingdom	Royal Marsden Hospital	Sutton
United States	University of Michigan	Ann Arbor	Michigan
United States	Baptist Lynn Cancer Institute	Boca Raton	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	National Jewish Health	Denver	Colorado
United States	City of Hope Duarte	Duarte	California
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	City of Hope Orange County Lennar Foundation Cancer Center	Irvine	California
United States	University of Kansas	Kansas City	Kansas
United States	City of Hope Long Beach Elm	Long Beach	California
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	NYU Langone Health Laura and Isaac Perlmutter Cancer Center	New York	New York
United States	Orlando Health	Orlando	Florida
United States	University of Pennsylvania Division of Hematology Oncology Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Providence Oncology and Hematology Care Clinic - Westside	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  China,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Poland,  Portugal,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For All Regions Other Than the European Union (EU) and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1	Ctrough is the observed serum concentration of Amivantamab at steady state on Cycle 4 Day 1 immediately prior to the next drug administration.	Cycle 4 Day 1 (28 days cycle)
Primary	For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1	Ctrough is the observed serum concentration of Amivantamab at pre-dose on Cycle 2 Day 1 immediately prior to the next drug administration.	Cycle 2 Day 1 (28 days cycle)
Primary	Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab of Cycle 2	AUC(Day 1-15) defined as area under the concentration time curve from Cycle 2 Day 1 to Day 15, will be reported.	Cycle 2 Day 1 to Cycle 2 Day 15 (28 days cycle)
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1).	Up to 1 year 11 months
Secondary	Progression-Free Survival (PFS)	PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, based on RECIST version 1.1.	Up to 1 year 11 months
Secondary	Duration of Response (DOR)	The DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR.	Up to 1 year 11 months
Secondary	Time to Response (TTR)	Time to response (that is time to first response) is defined as the time from the date of randomization to the date of first documentation of a response (PR or CR) prior to any disease progression and subsequent anticancer therapy, as defined by BICR using RECIST version 1.1., for participants who have PR or CR as their best response.	Up to 1 year 11 months
Secondary	Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention.	Up to 1 year 11 months
Secondary	Number of Participants with AEs by Severity	Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.	Up to 1 year 11 months
Secondary	Number of Participants with Clinical Laboratory Abnormalities	Number of participants with clinical laboratory abnormalities (serum Chemistry, hematology, coagulation, and urinalysis) will be reported.	Up to 1 year 11 months
Secondary	Number of Participants with Clinical Laboratory Abnormalities by Severity	Number of participants with clinical laboratory abnormalities by severity (serum Chemistry, hematology, coagulation, and urinalysis) will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.	Up to 1 year 11 months
Secondary	Number of Participants Infusion Related Reactions (IRRs)	Number of participants with IRRs will be reported.	Up to 1 year 11 months
Secondary	Number of Participants with Infusion Related Reactions (IRRs) by Severity	Number of participants with IRRs by severity will be reported.	Up to 1 year 11 months
Secondary	For All Regions Other Than the EU and Others Accepting Cycle 2 Day 1: Observed Serum Concentration (Ctrough) of Amivantamab at Pre-dose on Cycle 2 Day 1	The Ctrough is the observed serum concentration of Amivantamab at pre-dose on Cycle 2 Day 1 immediately prior to the next drug administration.	Cycle 2 Day 1 (28 days cycle)
Secondary	For EU and Any Applicable Region: Observed Serum Concentration (Ctrough) of Amivantamab at Steady State on Cycle 4 Day 1	The Ctrough is the observed serum concentration of Amivantamab at steady state on Cycle 4 Day 1 immediately prior to the next drug administration.	Cycle 4 Day 1 (28 days cycle)
Secondary	Model-Predicted Area Under the Concentration Time Curve from Day 1 to Day 15 (AUC[Day 1-15]) of Amivantamab at Steady State of Cycle 4	Model-predicted AUC(Day 1-15) defined as area under the concentration time curve from Cycle 4 Day 1 to Day 15, will be reported.	From Cycle 4 Day 1 to Cycle 4 Day 15 (28 days cycle)
Secondary	Percentage of Participants with Presence of Anti-amivantamab Antibodies and Anti-rHuPH20 Antibodies	Percentage of participants with presence of anti-amivantamab antibody anti-rHuPH20 antibodies will be reported.	Up to 1 year 11 months
Secondary	Percentage of Participants with Cancer Therapy Satisfaction as Assessed by Therapy Administration Satisfaction Questionnaire (TASQ)	Percentage of participants with cancer therapy satisfaction in will be assessed using the modified TASQ. The modified TASQ is an 11-item questionnaire measuring the impact of each mode of treatment administration on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction.	Up to 1 year 11 months
Secondary	Change from Baseline in TASQ as Assessed Over Time	Change from baseline in TASQ as assessed Over time will be reported. The modified TASQ is an 11-item questionnaire measuring the impact of each mode of treatment administration on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction.	Up to 1 year 11 months
Secondary	Participant Chair Time	Participant chair time will be assessed by time and motion analysis.	Up to 1 year 11 months
Secondary	Duration of Treatment Administration	Duration of treatment administration will be assessed by time and motion analysis.	Up to 1 year 11 months
Secondary	Active HCP Time For Drug Preparation, Treatment Administration and Posttreatment Monitoring	Active health care professional time for drug preparation, treatment administration, and posttreatment monitoring will be assessed by time and motion analysis.	Up to 1 year 11 months
Secondary	Participant Time in Treatment Room	Participant time in treatment room will be assessed by time and motion analysis.	Up to 1 year 11 months