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

Overview

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).

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, E and F) 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.

Interventions

• Biological Amivantamab IV
  Amivantamab will be administered as intravenous infusion.
• Biological Fluorouracil
  Fluorouracil will be administered as intravenous infusion.
• Biological Leucovorin
  Leucovorin will be administered as intravenous infusion.
• Biological Oxaliplatin
  Oxaliplatin will be administered as intravenous infusion.
• Biological Irinotecan
  Irinotecan will be administered as intravenous infusion.
• Biological Amivantamab
  Amivantamab will be administered.

Primary outcome measures

• Cohorts A, B, and C: Objective Response Rate (ORR) [Time frame: Up to 4 years 3 months]
• Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT) [Time frame: Up to 4 years 3 months]
• Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity [Time frame: Up to 4 years 3 months]
• Cohorts D and E: Number of Participants with Adverse Events (AE) [Time frame: Up to 4 years 3 months]
• Cohorts D and E: Number of Participants with Laboratory Values Abnormalities [Time frame: Up to 4 years 3 months]
• Cohorts D and E: Number of Participants with Vital Signs Abnormalities [Time frame: Up to 4 years 3 months]
• Cohorts F: Number of Participants with Adverse Events (AE) [Time frame: Up to 4 years 3 months]
• Cohorts F: Number of Participants with Laboratory Values Abnormalities [Time frame: Up to 4 years 3 months]
• Cohorts F: Number of Participants with Vital Signs Abnormalities [Time frame: Up to 4 years 3 months]

Secondary outcome measures (8)

• Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with AEs [Time frame: Up to 4 years 3 months]
• Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Laboratory Values Abnormalities [Time frame: Up to 4 years 3 months]
• Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Vital Signs Abnormalities [Time frame: Up to 4 years 3 months]
• Cohorts Ph1b-D, Ph1b-E, D, E and F: ORR [Time frame: Up to 4 years 3 months]
• Cohorts Ph1b-D, Ph1b-E, D, E and F: Duration of Response (DoR) [Time frame: Up to 4 years 3 months]
• Cohorts Ph1b-D, Ph1b-E, D, E and F: Disease Control Rate (DCR) [Time frame: Up to 4 years 3 months]
• Cohorts Ph1b-D, Ph1b-E, D, E and F: Clinical Benefit Rate (CBR) [Time frame: Up to 4 years 3 months]
• Cohorts D, E and F: Progression Free Survival (PFS) [Time frame: 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
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 14 centers

• O Neal Comprehensive Cancer Center at UAB — Birmingham
• University of Southern California — Los Angeles
• University of California, Los Angeles UCLA — Los Angeles
• Georgetown University Hospital — Washington D.C.
• H Lee Moffitt Cancer Center — Tampa
• University of Maryland School of Medicine — Baltimore
• University of Michigan Health System — Ann Arbor
• Start Midwest — Grand Rapids
• … and 6 more centers

Spain · 7 centers

• Hosp Univ Vall D Hebron — Barcelona
• Hosp. Gral. Univ. Gregorio Maranon — Madrid
• Hosp. Univ. Ramon Y Cajal — Madrid
• Hosp Univ Fund Jimenez Diaz — Madrid
• Hosp Univ Hm Sanchinarro — Madrid
• Hosp. Univ. Marques de Valdecilla — Santander
• Hosp. Clinico Univ. de Valencia — Valencia

Taiwan · 6 centers

• Changhua Christian Hospital — Changhua
• Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City
• Chi Mei Medical Center Liu Ying — Liou Ying Township
• National Cheng Kung University Hospital — Tainan
• National Taiwan University Hospital — Taipei
• Linkou Chang Gung Memorial Hospital — Taoyuan

South Korea · 5 centers

• Seoul National University Hospital — Seoul
• Severance Hospital Yonsei University Health System — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul
• The Catholic University of Korea Seoul St Mary s Hospital — Seoul

Belgium · 4 centers

• Institut Jules Bordet — Anderlecht
• Cliniques Universitaires Saint Luc — Brussels
• UZ Antwerpen — Edegem
• Universitair Ziekenhuis Gasthuisberg — Leuven

China · 4 centers

• The Second Hospital To Dalian Medical University — Dalian
• Sun Yat-sen University - The Sixth Affiliated Hospital Guangdong Gastrointestinal Hospital — Guangzhou
• The Second Affiliated Hospital of Zhejiang University College of Medicine — Hangzhou
• Hubei province tumor hospital — Wuhan

Canada · 3 centers

• BC Cancer Agency - Vancouver BC — Vancouver
• The Ottawa Hospital Cancer Centre — Ottawa
• Princess Margaret Cancer Centre University Health Network — Toronto

Italy · 3 centers

• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan
• A O Ospedale Niguarda Ca Granda — Milan
• Azienda Ospedaliero Universitaria Pisana — Pisa

Malaysia · 3 centers

• University Malaya Medical Centre — Kuala Lumpur
• Hospital Umum Sarawak — Kuching
• Beacon Hospital Sdn Bhd — Petaling Jaya

Germany · 2 centers

• Asklepios Klinik Altona — Hamburg
• Ludwig-Maximilians-Universitaet Muenchen — Munich

Puerto Rico · 2 centers

• Ad Vance Medical Research — Ponce
• Pan American Center for Oncology Trials LLC — Rio Piedras

Publications

• Oberstein PE, Hecht JR, Raghav K, Pietrantonio F, Arnold D, Moreno V, Van Cutsem E, Malik RA, Hong YS, Lee MA, Yu-Li Su H, Lee J, Chandana S, Cruz-Correa M, Yuan Y, Ahmad A, Lai KM, Hsu HC, Chen EX, Elez E, Lin CC, Lopez C, Prenen H, Rosello-Keranen S, Velez H, Yeh YM, Heinemann V, Eng C, Beom SH, Tejpar S, Chowdhury S, Lyu X, Kamat M, Curtin JC, Patel B, Xie J, Bhattacharya R, Schnepp RW, Yilmaz PMID 42013403

Identifiers

NCT: NCT05379595 · CR109215 · 61186372GIC2002 · 2021-006629-23 · 2023-506517-22-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗