A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer (NCT05379595) — Italy Trial Details

Condition(s) studied

Advanced or Metastatic Colorectal Cancer

Investigational drug(s) / intervention(s)

Amivantamab IV →Fluorouracil →Leucovorin →Oxaliplatin →Irinotecan →Amivantamab →

Amivantamab IV: Amivantamab will be administered as intravenous infusion.

Fluorouracil: Fluorouracil will be administered as intravenous infusion.

Leucovorin: Leucovorin will be administered as intravenous infusion.

Oxaliplatin: Oxaliplatin will be administered as intravenous infusion.

Irinotecan: Irinotecan will be administered as intravenous infusion.

Amivantamab: Amivantamab will be administered.

Study summary

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

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

No

Inclusion Criteria: * Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum * Participant must have tumor previously characterized as having wild-type Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), and without evidence of Erb-b2 receptor tyrosine kinase 2/human epidermal growth factor receptor 2 (ERBB2/HER2) amplification. Additional cohort-specific requirements: * Phase (Ph) 2 (Cohorts A, B, and C) Amivantamab monotherapy: Participant must have received at least 2 but not more than 3 prior lines of systemic therapy in the metastatic setting. Participant must have been diagnosed with left-sided colorectal cancer (CRC) (Cohort A and B) and right-sided (Cohort C)and have received or been intolerant to standard of care (SoC) fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and an anti-vascular endothelial growth factor (VEGF) treatment. Participant must be anti-EGFR treatment naive in Cohort A, an anti-epidermal growth factor receptor (EGFR) treatment Cohort B, with or without an anti-EGFR treatment in Cohort C * Ph 1b Dose Confirmation Cohorts (Ph1b-D and Ph1b-E), Ph2 (Cohorts D and E) Amivantamab+mFOLFOX6/FOLFIRI: Participant must been diagnosed with CRC and have received no more than 1 prior line of systemic therapy in the metastatic setting. Cohort Ph1b-D/Cohort D: Participant must be anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, and be eligible for treatment with mFOLFOX6 according to local regulatory approvals and SoC guidelines. Cohort Ph1b-E/Cohort E: Participant must be anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, and be eligible for treatment with FOLFIRI according to local regulatory approvals and SoC guidelines * Ph2 Cohorts F Amivantamab subcutaneous (SC) + mFOLFOX6: Participants must be treatment-naive for right-sided unresectable or metastatic CRC and be eligible for treatment with mFOLFOX6 according to local regulatory approvals and SoC guidelines * For Phase 1 dose confirmation cohorts (Cohorts Ph1b-D and Ph1b-E): Participant must have evaluable disease. For Phase 2: 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. Biopsies are required if clinically feasible for participants in Ph1b-D, Ph1b-E, and Cohort F. For Cohort F, archival tissue is required if a fresh biopsy is not feasible * 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: * Cohorts A, B, C, Ph1b-D, D, Ph1b-E, and E: 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; Cohort F: Participant with identified mutation in KRAS, NRAS, BRAF V600, or PTEN, identified fusions in ALK, ROS-1, RET, and NTRK 1, ERBB2/HER2 amplification, or identified to have MSI-H status by central 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 outcome measure(s)

Cohorts A, B, and C: Objective Response Rate (ORR) — Up to 4 years 3 months
ORR is defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), as defined by investigator assessment using Response Criteria in Solid Tumors (RECIST) version 1.1.
Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT) — Up to 4 years 3 months
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity — Up to 4 years 3 months
Number of participants with DLT by severity will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. Toxicities will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, graded as Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death related to adverse event.
Cohorts D and E: Number of Participants with Adverse Events (AE) — Up to 4 years 3 months
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the 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.
Cohorts D and E: Number of Participants with Laboratory Values Abnormalities — Up to 4 years 3 months
Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.
Cohorts D and E: Number of Participants with Vital Signs Abnormalities — Up to 4 years 3 months
Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.
Cohorts F: Number of Participants with Adverse Events (AE) — Up to 4 years 3 months
An AE is any untoward medical occurrence in a participant taking part in a in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the 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.
Cohorts F: Number of Participants with Laboratory Values Abnormalities — Up to 4 years 3 months
Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.
Cohorts F: Number of Participants with Vital Signs Abnormalities — Up to 4 years 3 months
Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.

Trial sites (53)

Facility	City	Region	Status
O Neal Comprehensive Cancer Center at UAB	Birmingham	Alabama	Completed
University of Southern California	Los Angeles	California	Completed
University of California, Los Angeles UCLA	Los Angeles	California	Recruiting
Georgetown University Hospital	Washington D.C.	District of Columbia	Completed
H Lee Moffitt Cancer Center	Tampa	Florida	Completed
University of Maryland School of Medicine	Baltimore	Maryland	Completed
University of Michigan Health System	Ann Arbor	Michigan	Recruiting
Start Midwest	Grand Rapids	Michigan	Completed
Hattiesburg Clinic	Hattiesburg	Mississippi	Recruiting
NYU Langone Long Island Clinical Research Associates	New York	New York	Recruiting
Herbert Irving Comprehensive Cancer Center Columbia University Medical Center	New York	New York	Recruiting
Stephenson Cancer Center	Oklahoma City	Oklahoma	Completed
Vanderbilt Ingram Cancer Center	Nashville	Tennessee	Recruiting
MD Anderson Cancer Center	Houston	Texas	Recruiting
Institut Jules Bordet	Anderlecht	Belgium	Recruiting
Cliniques Universitaires Saint Luc	Brussels	Belgium	Recruiting
UZ Antwerpen	Edegem	Belgium	Recruiting
Universitair Ziekenhuis Gasthuisberg	Leuven	Belgium	Recruiting
BC Cancer Agency - Vancouver BC	Vancouver	British Columbia	Completed
The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Recruiting
Princess Margaret Cancer Centre University Health Network	Toronto	Ontario	Recruiting
The Second Hospital To Dalian Medical University	Dalian	China	Completed
Sun Yat-sen University - The Sixth Affiliated Hospital Guangdong Gastrointestinal Hospital	Guangzhou	China	Recruiting
The Second Affiliated Hospital of Zhejiang University College of Medicine	Hangzhou	China	Recruiting
Hubei province tumor hospital	Wuhan	China	Recruiting
Asklepios Klinik Altona	Hamburg	Germany	Recruiting
Ludwig-Maximilians-Universitaet Muenchen	Munich	Germany	Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori	Milan	Italy	Recruiting
A O Ospedale Niguarda Ca Granda	Milan	Italy	Recruiting
Azienda Ospedaliero Universitaria Pisana	Pisa	Italy	Recruiting
University Malaya Medical Centre	Kuala Lumpur	Malaysia	Recruiting
Hospital Umum Sarawak	Kuching	Malaysia	Recruiting
Beacon Hospital Sdn Bhd	Petaling Jaya	Malaysia	Recruiting
Ad Vance Medical Research	Ponce	Puerto Rico	Recruiting
Pan American Center for Oncology Trials LLC	Rio Piedras	Puerto Rico	Recruiting
Seoul National University Hospital	Seoul	South Korea	Recruiting
Severance Hospital Yonsei University Health System	Seoul	South Korea	Recruiting
Asan Medical Center	Seoul	South Korea	Recruiting
Samsung Medical Center	Seoul	South Korea	Recruiting
The Catholic University of Korea Seoul St Mary s Hospital	Seoul	South Korea	Recruiting

+ 13 more sites — see the full list on the official registry below.

More Janssen Research & Development, LLC trials in Italy

Nipocalimab in Moderate to Severe Sjogren's Disease Active, not recruiting

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 Active, not recruiting

A Study Comparing JNJ-79635322 and an Anti-B-cell Maturation Antigen (BCMA)xCD3 Bispecific Antibody in Participants With Relapsed or Refractory Multiple Myeloma Recruiting

A Study of JNJ-79635322 in Participants With Relapsed or Refractory Multiple Myeloma Active, not recruiting

A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer Active, not recruiting