RightFit
RecruitingPhase 1 / Phase 2

A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 28 days, 30 days
  • Procedures mentioned: Physical exams

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests amivantamab alone or with standard chemotherapy for colon or rectal cancer that cannot be removed by surgery or has spread. It looks at how well treatment fights cancer, its safety, and the dose to use with chemotherapy.

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).

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have colon or rectal adenocarcinoma, a type of cancer, confirmed by a tissue or cell test. The cancer cannot be removed by surgery or has spread.
  • Earlier tumor tests must show no KRAS, NRAS, or BRAF gene changes and no extra copies of the HER2 gene.
  • For amivantamab alone: have had 2–3 treatment plans for cancer that has spread. You must have received, or been unable to tolerate, the listed standard chemotherapy and VEGF-blocking treatment, which targets blood vessel growth. Groups also have rules about where the cancer started and past EGFR-blocking treatment.
  • For groups D and E: have had no more than 1 treatment plan for cancer that has spread and no EGFR-blocking treatment. Group D requires no past oxaliplatin for cancer that has spread and ability to receive mFOLFOX6 chemotherapy. Group E requires no past irinotecan for cancer that has spread and ability to receive FOLFIRI chemotherapy.
  • For group F: have untreated cancer on the right side of the colon that cannot be removed by surgery or has spread, and be able to receive mFOLFOX6 chemotherapy.
  • Have cancer doctors can assess in phase 1 or measure on scans in phase 2. Be fully active or able to do light work despite some limits on hard physical activity.
  • Agree to a biopsy, which removes a small tumor sample. For phase 1b groups and group F, this is required only if medically possible. Group F needs a stored tumor sample if a new biopsy is not possible.
  • If you can become pregnant, have negative blood pregnancy tests before treatment and agree to more tests during the study. You must not be pregnant, breastfeeding, or planning pregnancy during the study.

Who can't join

  • For all groups except F: screening blood tests find KRAS, NRAS, BRAF, or certain EGFR gene changes, or extra HER2 gene copies.
  • For group F: screening blood tests find KRAS, NRAS, BRAF V600, or PTEN gene changes; joined ALK, ROS-1, RET, or NTRK1 genes; extra HER2 gene copies; or MSI-H, a sign of many changes in the tumor's DNA.
  • Have cancer in the brain that causes symptoms or has not been treated.
  • Have or have had cancer in the layers around the brain and spinal cord.
  • Have another condition that the study doctor thinks could make joining unsafe or interfere with study tests.

Simplified for readability. The official criteria below are what the study team uses.

Official 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

Study sites (14)

AL

CA

DC

FL

MD

MI

MS

NY

OK

TN

TX