Clinical trial NCT06750094: A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy
Official title: A Randomized, Open-label Phase 3 Study of Amivantamab + FOLFIRI Versus Cetuximab/Bevacizumab + FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Recurrent, Unresectable or Metastatic Colorectal Cancer Who Have Received Prior Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Colorectal Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2024-12-27
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare how long the participants are disease-free (progression-free survival) and and the length of time until a participant dies (overall survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or metastatic colorectal cancer who have previously received chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Participants must have recurrent, unresectable or metastatic disease
* Be diagnosed to have KRAS, NRAS, and BRAF wild-type (WT) tumor as determined by local testing
* Must agree to the submission of fresh or archival tumor tissue post-progression from the most recent therapy, if clinically feasible
* Have measurable disease according to RECIST v1.1
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
* Participant must have received 1 line of systemic therapy (fluoropyrimidine-based and oxaliplatin-based) for metastatic colorectal cancer (mCRC), with documented radiographic disease progression on or after this line of therapy

Exclusion Criteria:

* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: amivantamab, cetuximab or bevacizumab or any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status who has not received immunotherapy treatments
* Participant with known human epidermal growth factor receptor 2 (HER2)- positive/amplified tumor
* Has prior exposure to irinotecan, any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET)

Primary outcomes:
measure: Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: Up to 2 years 1 month
measure: Overall Survival (OS)
timeFrame: Up to 4 years 4 months
Secondary outcomes:
measure: Objective Response Rate (ORR) as Assessed by BICR
timeFrame: Up to 4 years 4 months
measure: Progression Free Survival as Assessed by Investigator
timeFrame: Up to 4 years 4 months
measure: Objective Response Rate as Assessed by Investigator
timeFrame: Up to 4 years 4 months
measure: Duration of Response (DoR) as Assessed by BICR
timeFrame: Up to 4 years 4 months
measure: Duration of Response as Assessed by Investigator
timeFrame: Up to 4 years 4 months
measure: Progression Free Survival After Subsequent Therapy (PFS2)
timeFrame: Up to 4 years 4 months
measure: Disease Control Rate (DCR) as Assessed by BICR
timeFrame: Up to 4 years 4 months
measure: Disease Control Rate as Assessed by Investigator
timeFrame: Up to 4 years 4 months
measure: Time to Treatment Failure
timeFrame: Up to 4 years 4 months
measure: Curative Resection (R0) Rate
timeFrame: Up to 4 years 4 months
measure: Number of Participants with Adverse Events (AEs) by Severity
timeFrame: Up to 4 years 4 months
measure: Number of Participants with Abnormalities in Laboratory Values
timeFrame: Up to 4 years 4 months
measure: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
timeFrame: From baseline up to 4 years 4 months
measure: Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30
timeFrame: Up to 4 years 4 months
measure: Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C29) Score
timeFrame: From baseline up to 4 years 4 months
measure: Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C29 Score
timeFrame: Up to 4 years 4 months
measure: Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score
timeFrame: Up to 4 years 4 months
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Center
state: Arizona
city: Prescott
country: United States
facility: Arizona Oncology Associates PC NAHOA
state: Arizona
city: Jonesboro
country: United States
facility: St. Bernard's Medical Center
state: Arkansas
city: Bakersfield
country: United States
facility: CBCC Global Research
state: California
city: Glendale
country: United States
facility: Los Angeles Cancer Network
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation
state: California
city: Torrance
country: United States
facility: Torrance Memorial Physicians Network
state: California
city: Aurora
country: United States
facility: University of Colorado Denver Anschultz Medical Campus
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Norwich
country: United States
facility: Eastern Connecticut Hematology & Oncology Assoc.
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists South
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center Campus
state: Florida
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists North Region
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists East
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute Emory University
state: Georgia
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: MedStar Franklin Square Medical Center
state: Maryland
city: Grand Rapids
country: United States
facility: Cancer And Hematology Centers of Western Michigan PC
state: Michigan
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Einstein Comprehensive Cancer Center
state: New York
city: Mineola
country: United States
facility: Perlmutter Cancer Center at NYU Long Island
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center NYU Hematology Associates
state: New York
city: Shirley
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Cleveland
country: United States
facility: University Hospital of Cleveland
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Abilene
country: United States
facility: Texas Oncology West Texas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology DFW
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio
state: Texas
city: Temple
country: United States
facility: Scott And White Memorial Hospital
state: Texas
city: Lacey
country: United States
facility: Providence Regional Cancer System
state: Washington
city: Concord
country: Australia
facility: Concord Hospital
city: Heidelberg
country: Australia
facility: Warringal Private Hospital
city: South Woodville
country: Australia
facility: Queen Elizabeth Hospital
city: St Albans
country: Australia
facility: Western Health Sunshine Hospital
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Haine Saint Paul La Louviere
country: Belgium
facility: Jolimont
city: Kortrijk
country: Belgium
facility: Az Groeninge
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Barretos
country: Brazil
facility: Fundacao Pio XII
city: Caxias do Sul
country: Brazil
facility: Fundacao Universidade de Caxias do Sul
city: Jau
country: Brazil
facility: Fundacao Doutor Amaral Carvalho
city: Salvador
country: Brazil
facility: Hospital Santa Izabel Santa Casa de Misericordia da Bahia
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional De Medicina S Jose Rio Preto Hospital De Base
city: Sao Paulo
country: Brazil
facility: Fundacao Antonio Prudente A C Camargo Cancer Center
city: Vitoria
country: Brazil
facility: Associacao Feminina de Educacao e Combate ao Cancer Hospital Santa Rita de Cassia
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Beijing Friendship Hospital Capital Medical University
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Ganzhou
country: China
facility: Ganzhou Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital Sun Yat sen University
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin medical university cancer hospital
city: Huizhou
country: China
facility: Huizhou Central People's Hospital
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of NanChang University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Avignon Cedex 9
country: France
facility: Institut Sainte Catherine
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Poitiers Cedex
country: France
facility: CHU De Poitiers
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin Campus Virchow Klinikum
city: Frankfurt am Main
country: Germany
facility: Krankenhaus NorthWest
city: Heidelberg
country: Germany
facility: National Center for Tumor Diseases NCT
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince Of Wales Hospital
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatokorhaz es Rendelointezet
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem
city: Delhi
country: India
facility: Rajiv Gandhi Cancer Institute and Research Centre
city: Hyderabad
country: India
facility: Asian Institute Of Gastroenterology
city: Kolkata
country: India
facility: B P Poddar Hospital and Medical research Limited
city: Mumbai
country: India
facility: Tata Memorial Hospital
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital and Research Centre
city: Varanasi
country: India
facility: Mahamana Pandit Madan Mohan Malviya Cancer Centre
city: Vellore
country: India
facility: Christian medical
city: Beer Yaakov
country: Israel
facility: Yitzhak Shamir Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Assuta MC
city: Milano
country: Italy
facility: Istituto Dei Tumori Di Milano
city: Padova
country: Italy
facility: Istituto Oncologico Veneto - IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale ASU FC
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Nagoya Shi
country: Japan
facility: Aichi Cancer Center
city: Osaka City
country: Japan
facility: Osaka International Cancer Institute
city: Osaka Sayama shi
country: Japan
facility: Kindai University Hospital
city: Osaka-Shi
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Suita-shi
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Mary s Hospital
city: Georgetown
country: Malaysia
facility: Hospital Pulau Pinang
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: Putrajaya
country: Malaysia
facility: Institut Kanser Negara Clinical Research Center
city: Chihuahua
country: Mexico
facility: Centro Oncologico de Chihuahua
city: Ciudad de Mexico
country: Mexico
facility: Centro Oncologico Personalizado Cope S De R L De C V
city: Guadalajara
country: Mexico
facility: Actualidad Basada En La Investigacion Del Cancer
city: Puebla
country: Mexico
facility: Oncocenter
city: Queretaro
country: Mexico
facility: Cuidados Oncologicos
city: Queretaro
country: Mexico
facility: Health Pharma Queretaro SA de CV
city: Tijuana
country: Mexico
facility: COI Centro Oncologico Internacional Tijuana
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Tilburg
country: Netherlands
facility: ETZ TweeSteden
city: Biala Podlaska
country: Poland
facility: Wojewodzki Szpital Specjalistyczny
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologii im Marii Sklodowskiej Curie w Bialymstoku
city: Brzozow
country: Poland
facility: Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz w Gliwicach
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Olsztyn
country: Poland
facility: SPZOZ Ministerstwa Spraw Wewnetrznych z Warminsko Mazurskim Centrum Onkologii w Olsztynie
city: Opole
country: Poland
facility: SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarowskiego
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
city: San Juan
country: Puerto Rico
facility: Pan American Center for Oncology Trials LLC
city: Brasov
country: Romania
facility: Centrul Medical Unirea SRL
city: Bucuresti
country: Romania
facility: Ponderas Academic Hospital
city: Craiova
country: Romania
facility: Clinica de Oncologie Sf Nectarie
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Lund
country: Sweden
facility: Skanes universitetssjukhus
city: Stockholm
country: Sweden
facility: Sodersjukhuset
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Uppsala
country: Sweden
facility: Uppsala University
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
city: Songkhla
country: Thailand
facility: Songklanagarind hospital
city: Adana
country: Turkey
facility: Adana City Hospital
city: Ankara
country: Turkey
facility: Gulhane Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital
city: Ankara
country: Turkey
facility: Gazi University Hospital
city: Istanbul
country: Turkey
facility: Bakirkoy Training and Research Hospital
city: İstanbul
country: Turkey
facility: Marmara University Pendik Training Hospital
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram Medical Faculty
city: Sakarya
country: Turkey
facility: Sakarya University Training and Research Hospital
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: