What side effects are associated with this type of intervention?

Common treatments for colorectal cancer that target EGFR and MET receptors, such as amivantamab, include monoclonal antibodies like cetuximab and panitumumab. The known side effects of these treatments often include skin rash, diarrhea, nausea, and neutropenia. Additionally, severe adverse events such as hypertension and digestive issues have been reported with combination therapies involving these agents. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

FDA-approved treatments for colorectal cancer include various targeted therapies and chemotherapies. Notably, cetuximab and panitumumab are monoclonal antibodies targeting the EGFR receptor, similar to one of the targets of amivantamab. These drugs are used in combination with chemotherapy for metastatic colorectal cancer. Additionally, bevacizumab, an anti-VEGF monoclonal antibody, is approved for use with chemotherapy in colorectal cancer. While there are no FDA-approved therapies specifically targeting both EGFR and MET receptors like amivantamab, the existing approvals highlight the role of targeted therapies in colorectal cancer treatment.

What other types of research exist?

Promising novel alternatives to Amivantamab for colorectal cancer patients include: 1) Pembrolizumab (an immune checkpoint inhibitor) which has shown efficacy in various cancers including CRC, particularly in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. 2) Regorafenib, an orally active inhibitor of multiple kinases involved in tumor angiogenesis, oncogenesis, and the tumor microenvironment. 3) Combination therapies involving immune checkpoint inhibitors and other agents, such as nivolumab plus ipilimumab, which are being explored in clinical trials for their synergistic effects. These alternatives offer different mechanisms of action and may provide additional options for CRC patients.

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Monoclonal Antibodies

Amivantamab + Chemotherapy for Colorectal Cancer (OrigAMI-1 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum

Must not have

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

History or known presence of leptomeningeal disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years 3 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new medicine called amivantamab on patients with advanced colorectal cancer. The medicine helps the immune system find and destroy cancer cells. Researchers want to see how well it works alone and with standard chemotherapy.

Who is the study for?

This trial is for adults with advanced colorectal cancer that can't be removed by surgery or has spread. They must have a specific performance status, agree to a tumor biopsy, and not be pregnant. People with certain genetic mutations or brain metastasis are excluded.

What is being tested?

The study tests amivantamab alone and alongside standard chemotherapy (Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan) in patients with metastatic colorectal cancer. It aims to find the safest dose when combined with chemo and measure its effectiveness against tumors.

What are the potential side effects?

Amivantamab may cause side effects like infusion reactions (symptoms at the site of injection), skin rash, fatigue, and possibly affect liver function. Standard chemotherapy can lead to nausea, hair loss, nerve damage, diarrhea, and low blood cell counts.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have been diagnosed with a type of colon or rectal cancer that cannot be removed by surgery.

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I agree to have a biopsy of my tumor as required by the study.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer has a specific mutation identified through a blood test.

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I have a history of cancer spreading to the lining of my brain and spinal cord.

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I have brain metastasis that is causing symptoms or hasn't been treated.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 years 3 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 years 3 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 years 3 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cohorts A, B, and C: Objective Response Rate (ORR)

Cohorts D and E: Number of Participants with Adverse Events (AE)

Cohorts D and E: Number of Participants with Laboratory Values Abnormalities

+3 more

Secondary study objectives

Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with AEs

Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Laboratory Values Abnormalities

Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Vital Signs Abnormalities

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Cohorts A, B, and C: Amivantamab MonotherapyExperimental Treatment1 Intervention

Participants with left-sided colorectal cancer (CRC) in Cohort A (no prior anti-epidermal growth factor receptor \[EGFR\] therapy) and in Cohort B (post anti-EGFR therapy), and right-sided CRC in Cohort C (with or without anti-EGFR therapy), will be administered intravenous (IV) infusion of amivantamab 1050 milligrams (mg) if body weight (BW) is less than (\<) 80 kilograms (kg) or 1400 mg if BW is greater than or equal to (\>=) 80 kg, as monotherapy on Days 1 and 15 of Cycle 2 (28-days cycle).

Group II: Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI)Active Control4 Interventions

Participants who are anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab along with FOLFIRI SOC chemotherapy on Days -1, -2, and 8 of Cycle 1 and Days 1 and 15 of Cycle 2 in Ph1b-E. For Cohort E, RP2CD determined in Ph1b-E will be administered.

Group III: Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6)Active Control4 Interventions

Participants who are anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab 1050 or 700 mg (dose level 0 \[DL0\]) if BW is \<80 kg, or 1400 or 1050 mg (dose de-escalation \[DL-1\]) if BW is \>= 80 kg, on Days -1, -2, 8 and 22 of Cycle 1 and along with mFOLFOX6 SOC chemotherapy on Days 1 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 (each cycle of 28 days) in Phase 1b dose confirmation Cohort (Cohort Ph1b-D). Participant in Phase 2 Cohort (Cohort D) will receive recommended Phase 2 combination dose (RP2CD) of amivantamab along with mFOLFOX6 SOC chemotherapy determined in Cohort Ph1b-D.

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for colorectal cancer often involve targeted therapies that focus on specific molecular pathways. Amivantamab, a bispecific antibody, targets both EGFR and MET receptors, which are involved in tumor growth and survival. Similarly, cetuximab and panitumumab target the EGFR pathway, inhibiting cancer cell proliferation. Bevacizumab targets VEGF, reducing tumor blood supply and growth. These targeted treatments are crucial for colorectal cancer patients as they provide more personalized and effective options, particularly for those with specific genetic profiles, leading to better outcomes and fewer side effects compared to traditional chemotherapy.

[Personalized tumor therapy for gastrointestinal tumors].Medical treatment of advanced colorectal cancer in 2009.