1000 Participants Needed

Amivantamab + Chemotherapy vs Cetuximab + Chemotherapy for Colorectal Cancer

(OrigAMI-2 Trial)

Recruiting at 276 trial locations
SC
Overseen ByStudy Contact
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Janssen Research & Development, LLC
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how long individuals with a specific type of colorectal cancer can remain disease-free when treated with different drug combinations. One group will receive amivantamab (a monoclonal antibody) with chemotherapy, while another group will receive cetuximab (another monoclonal antibody) with chemotherapy. The trial focuses on individuals with left-sided colorectal cancer that cannot be surgically removed or has metastasized, and who have specific genetic profiles (KRAS, NRAS, and BRAF wild-type). Participants must have a confirmed diagnosis of this cancer type that impacts their daily life. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amivantamab, when combined with chemotherapy, has helped about 49% of people with metastatic colorectal cancer experience some tumor shrinkage. Nearly half of the patients saw their tumors get smaller. Testing has confirmed its safety both on its own and with standard chemotherapy. Results suggest it is generally well-tolerated, though, like any treatment, it can have side effects.

Cetuximab is an approved treatment for certain colorectal cancers. Studies have found it is usually well-tolerated, but serious side effects, such as infusion reactions, occurred in about 3% of patients. These reactions can be severe, so discussing them with a healthcare provider is important.

Both treatments have undergone safety studies. Those considering joining a trial should discuss the possible risks and benefits with a doctor.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about amivantamab for colorectal cancer because it offers a novel approach by targeting both the EGFR and MET pathways, which are often involved in cancer growth and resistance to treatment. This dual targeting could potentially overcome some of the limitations of current therapies, such as cetuximab, which primarily focuses on the EGFR pathway alone. Additionally, amivantamab is an antibody treatment, providing a new active ingredient that could enhance treatment effectiveness compared to existing options. This combination of mechanisms gives hope for improved outcomes for patients facing this challenging condition.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

This trial will compare two treatment options for colorectal cancer. Studies have shown that amivantamab, which participants in this trial may receive with chemotherapy, helps nearly half of the patients with metastatic colorectal cancer by reducing their cancer. In another study, patients taking amivantamab with chemotherapy had stable cancer for about 5.7 months on average, meaning the cancer did not worsen during this time. Meanwhile, cetuximab, another treatment option in this trial used with chemotherapy, has been shown to help patients with advanced colorectal cancer live longer. However, about 30% of patients with cancer on the left side of the colon do not respond to cetuximab, meaning their cancer does not shrink or slow down. Both treatments offer hope, but their effectiveness can vary from person to person.12678

Who Is on the Research Team?

JR

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with left-sided colorectal cancer that's spread and can't be removed by surgery. They must have a type of tumor without certain mutations (KRAS/NRAS/BRAF wild-type), be able to provide a fresh tissue sample, have measurable disease, and be in good physical condition (ECOG 0 or 1).

Inclusion Criteria

Have measurable disease according to RECIST v1.1
I agree to provide a fresh sample of my tumor for testing.
I am fully active or restricted in physically strenuous activity but can do light work.
See 2 more

Exclusion Criteria

Has known allergies, hypersensitivity, or intolerance to specific excipients
I have a history of lung conditions not caused by infections.
I have or had another type of cancer besides the one currently being treated.
See 2 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amivantamab or cetuximab in combination with chemotherapy (mFOLFOX6 or FOLFIRI) for 28-day treatment cycles until disease progression or other discontinuation criteria are met

Up to 4 years and 2 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 years 3 months

What Are the Treatments Tested in This Trial?

Interventions

  • Amivantamab
  • Cetuximab
Trial Overview The study compares two treatments: Amivantamab combined with chemotherapy (mFOLFOX6 or FOLFIRI) versus Cetuximab with the same chemo options. The goal is to see which treatment keeps the disease from worsening longer.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A: Amivantamab in Combination With ChemotherapyExperimental Treatment5 Interventions
Group II: Arm B: Cetuximab in Combination With ChemotherapyActive Control5 Interventions

Amivantamab is already approved in United States, European Union for the following indications:

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Approved in United States as Rybrevant for:
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Approved in European Union as Rybrevant for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials
1,022
Recruited
6,408,000+
Joaquin Duato profile image

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD profile image

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

The CIFRA study is investigating the effectiveness of cetuximab combined with irinotecan and fluorouracil in patients with metastatic colorectal cancer who have a specific genetic profile (FcγRIIIa V/V), which may enhance the drug's action through a mechanism called Antibody-Dependent Cell-mediated Cytotoxicity (ADCC).
This phase II trial aims to determine if patients with the FcγRIIIa V/V genotype have a higher response rate to cetuximab, potentially improving treatment outcomes, while also assessing safety and survival metrics.
Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol.Ottaiano, A., Scala, S., Normanno, N., et al.[2020]
In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.
The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.
A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer.Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]
In a study of 146 patients with metastatic colorectal cancer, those with left-sided primary tumors experienced significantly longer overall survival (OS) and progression-free survival (PFS) compared to those with right-sided tumors, particularly among patients with KRAS wild-type mutations.
The results suggest that the location of the primary tumor and the KRAS mutation status interact to influence treatment outcomes, indicating that left-sided tumors may predict better efficacy of cetuximab-based therapies.
Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial.von Einem, JC., Heinemann, V., von Weikersthal, LF., et al.[2022]

Citations

RYBREVANT® (amivantamab-vmjw) plus chemotherapy ...RYBREVANT® (amivantamab-vmjw) plus chemotherapy show 49 percent overall response rate in metastatic colorectal cancer. Median duration of ...
Amivantamab with or without chemotherapy in right-sided ...In pts receiving ami plus FOLFOX or FOLFIRI, ORR was 43% (3/7) and DCR was 86% (6/7). Median DoR is 5.8 mo, with all 3 responders on treatment, ...
Dr Pietrantonio on Future Directions of Evaluating ...At a median follow-up of 8.2 months (range, 3.2-11.9) in the amivantamab plus FOLFOX or FOLFIRI arm, patients (n = 7) experienced an ORR of 43% ...
Use of RYBREVANT in Colorectal Cancer - OrigAMI-1 StudyMedian progression-free survival (PFS) was 5.7 months, not estimable (NE), 4.6 months, and 3.6 months, and overall response rates (ORRs) were 29 ...
Results From Amivanatamab Clinical Trial for Metastatic ...Dirk Arnold, MD, PhD, discusses results from the OrigAMI-1 clinical trial in left-sided RAS/BRAF wild-type metastatic colorectal cancer.
NCT05379595 | A Study of Amivantamab Monotherapy ...The safety of amivantamab as a monotherapy or in addition to SoC chemotherapy will be assessed by physical examinations, Eastern Cooperative Oncology Group ( ...
RYBREVANT® (amivantamab-vmjw)An overview of the PALOMA study evaluating the safety, PK, and efficacy of amivantamab SC in patients with advanced solid malignancies.
OrigAMI-1, an open-label, phase 1b/2 study.Ami monotherapy demonstrated promising, durable antitumor activity in refractory mCRC, including pts treated with prior anti-EGFR therapy and pts with right- ...
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