Clinical trial NCT05379595: A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer
Official title: A Phase 1b/2, Open-Label Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced or Metastatic Colorectal Cancer
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-05-18
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the anti-tumor activity of amivantamab as a monotherapy (Cohorts A, B, and C), to characterize the safety of amivantamab when added to standard-of care (SoC) chemotherapy in participants with metastatic colorectal cancer (mCRC) (Ph2 cohorts), and to assess the recommended phase 2 combination dose (RP2CD) of amivantamab when added to SoC chemotherapy (Ph1b cohorts).

Detailed description: Colorectal cancer (CRC) is a major global health concern and the third most common cancer worldwide. Amivantamab (also known as RYBREVANT or JNJ-61186372) is a fully human immunoglobulin (Ig) G1-based bispecific antibody (Ab) directed against the epidermal growth factor (EGF) and mesenchymal epithelial transition (MET) receptors, with evidence of preclinical activity against non-small cell lung cancer (NSCLC) tumors with activating EGF receptor (EGFR) mutations, the T790M and C797S second-site resistance EGFR mutations, overexpressed wild-type EGFR, as well as with activation of the MET pathway. Amivantamab has demonstrated activity in both EGFR- and MET-driven NSCLC, with preclinical evidence demonstrating its ability to recruit immune effector cells. While two anti-EGFR antibodies are incorporated as part of the SoC for CRC patients, MET is highly expressed or amplified in subsets of CRC and additionally plays a role in mediating resistance to anti-EGFR treatments. The study consists of up to 28 days screening period, treatment period will begin on Cycle 1 Day 1 (C1D1) (for Cohorts A, B, and C) or C1D -2 (for Ph1b-D, Ph1b-E, Cohorts D and E) with the administration of the study treatment and continue as 28-day cycles until the end of treatment visit, up to 30 days after discontinuation of study treatment. The safety of amivantamab as a monotherapy or in addition to SoC chemotherapy will be assessed by physical examinations, Eastern Cooperative Oncology Group (ECOG) criteria for performance status (PS), laboratory tests, vital signs, monitoring of adverse events, and concomitant medication usage. The total duration of this study will be up to 4 years 3 months.

Eligibility criteria: Inclusion Criteria:

* Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum
* For Phase 1 dose confirmation cohorts (Cohorts Ph1b-D and Ph1b-E): Participant must have evaluable disease. For Phase 2 dose expansion cohorts (Cohorts D and E): Participant must have measurable disease according to Response Criteria in Solid Tumors (RECIST) Version 1.1. If only one measurable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed greater than or equal to (\>=) 7 days after the biopsy
* Participant must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Participant must have a tumor lesion amenable for biopsy and agree to mandatory protocol-defined screening biopsy
* A female participant of childbearing potential must have a negative serum pregnancy 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. Note: Participant must not be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study

Exclusion Criteria:

* Participant with identified mutation in Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), or epidermal growth factor receptor (EGFR) ectodomain, or ERBB2/HER2 amplification by central circulating tumor deoxyribonucleic acid (ctDNA) testing at screening
* Participant with symptomatic or untreated brain metastasis
* History or known presence of leptomeningeal disease
* Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Primary outcomes:
measure: Cohorts A, B, and C: Objective Response Rate (ORR)
timeFrame: Up to 4 years 3 months
measure: Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT)
timeFrame: Up to 4 years 3 months
measure: Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity
timeFrame: Up to 4 years 3 months
measure: Cohorts D and E: Number of Participants with Adverse Events (AE)
timeFrame: Up to 4 years 3 months
measure: Cohorts D and E: Number of Participants with Laboratory Values Abnormalities
timeFrame: Up to 4 years 3 months
measure: Cohorts D and E: Number of Participants with Vital Signs Abnormalities
timeFrame: Up to 4 years 3 months
Secondary outcomes:
measure: Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with AEs
timeFrame: Up to 4 years 3 months
measure: Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Laboratory Values Abnormalities
timeFrame: Up to 4 years 3 months
measure: Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Vital Signs Abnormalities
timeFrame: Up to 4 years 3 months
measure: Cohorts Ph1b-D, Ph1b-E, D, and E: ORR
timeFrame: Up to 4 years 3 months
measure: Cohorts Ph1b-D, Ph1b-E, D, and E: Duration of Response (DoR)
timeFrame: Up to 4 years 3 months
measure: Cohorts Ph1b-D, Ph1b-E, D, and E: Clinical Benefit Rate (CBR)
timeFrame: Up to 4 years 3 months
measure: Cohorts D and E: Progression Free Survival (PFS)
timeFrame: Up to 4 years 3 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: O Neal Comprehensive Cancer Center at UAB
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles UCLA
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Start Midwest
state: Michigan
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: New York
country: United States
facility: NYU Langone Long Island Clinical Research Associates
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center Columbia University Medical Center
state: New York
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Gasthuisberg
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver BC
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Da Lian Shi
country: China
facility: The Second Hospital To Dalian Medical University
city: Guangzhou
country: China
facility: Sun Yat-sen University - The Sixth Affiliated Hospital Guangdong Gastrointestinal Hospital
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University College of Medicine
city: Wu Han Shi
country: China
facility: Hubei province tumor hospital
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Munich
country: Germany
facility: Ludwig-Maximilians-Universitaet Muenchen
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: A O Ospedale Niguarda Ca Granda
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
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: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: Petaling Jaya
country: Malaysia
facility: Beacon Hospital Sdn Bhd
city: Ponce
country: Puerto Rico
facility: Ad Vance Medical Research
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials LLC
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 Fund Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp Univ Hm Sanchinarro
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Liou Ying Township
country: Taiwan
facility: Chi Mei Medical Center Liu Ying
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: