Amivantamab + FOLFIRI for Colorectal Cancer

(OrigAMI-3 Trial)

Recruiting at 148 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Janssen Research & Development, LLC

Must not be taking: Irinotecan, EGFR agents, MET agents

Disqualifiers: ILD, Second malignancy, HER2-positive, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare how long the participants are disease-free (progression-free survival) and and the length of time until a participant dies (overall survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or metastatic colorectal cancer who have previously received chemotherapy.

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.

What data supports the effectiveness of the drug combination Amivantamab and Cetuximab for colorectal cancer?

Research shows that adding cetuximab to the FOLFIRI regimen (a combination of chemotherapy drugs) significantly improves survival and response rates in patients with a specific type of colorectal cancer. This suggests that cetuximab, when combined with other treatments, can be effective in managing colorectal cancer. ^{1 2 3 4 5}

Is the combination of Amivantamab and FOLFIRI safe for humans?

The safety of cetuximab, a drug similar to Amivantamab, has been studied in combination with various chemotherapy regimens like FOLFOX and CAPIRI for colorectal cancer. These studies generally found that the combination was safe, but patients experienced some side effects like skin reactions and diarrhea. ^{2 6 7 8 9}

How is the drug Amivantamab + FOLFIRI unique for treating colorectal cancer?

The combination of Amivantamab with FOLFIRI for colorectal cancer is unique because it includes Amivantamab, a newer drug that targets specific proteins involved in cancer growth, potentially offering a novel mechanism of action compared to traditional chemotherapy regimens. This approach may provide an alternative for patients with specific genetic profiles, such as those with KRAS wild-type tumors, where other treatments like cetuximab have shown effectiveness. ^{3 5 10 11 12}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for people with a specific type of colorectal cancer that hasn't changed certain genes called KRAS/NRAS and BRAF. Participants should have already tried chemotherapy but still have cancer that can't be removed by surgery or has spread.

Inclusion Criteria

My colon or rectum cancer has returned, can't be removed, or has spread.

My tumor is KRAS, NRAS, and BRAF wild-type.

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

Exclusion Criteria

My cancer is MSI-H/dMMR and I haven't had immunotherapy.

I have been treated with drugs targeting EGFR or MET, or have received irinotecan.

I have or might have a lung condition not caused by an infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Amivantamab + FOLFIRI or Cetuximab/Bevacizumab + FOLFIRI in 28-day cycles until disease progression or other discontinuation criteria are met

Up to 2 years 1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years 4 months

Treatment Details

Interventions

• Amivantamab (Monoclonal Antibodies)
• Cetuximab (Monoclonal Antibodies)

Trial Overview The study tests if Amivantamab combined with FOLFIRI chemotherapy works better than the usual treatment, either Cetuximab or Bevacizumab with FOLFIRI, in extending the time patients live without their disease getting worse and overall survival time.

Participant Groups

Group I: Arm A: Amivantamab + FOLFIRI Experimental Treatment 4 Interventions

Participants will receive amivantamab along with FOLFIRI (consisting of 5-fluorouracil, leucovorin calcium \[folinic acid\] or levoleucovorin, and irinotecan) as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.

Group II: Arm B: Cetuximab or Bevacizumab + FOLFIRI Active Control 5 Interventions

Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

The combination of FOLFOXIRI and bevacizumab demonstrated a promising progression-free survival (PFS) rate of 74% at 10 months in patients with unresectable metastatic colorectal cancer, based on a phase 2 study involving 57 patients.

The treatment was found to be safe, with no unexpected adverse events reported, although common serious side effects included neutropenia and hypertension, indicating that while effective, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Masi, G., Loupakis, F., Salvatore, L., et al.[2022]

The combination of cetuximab with oxaliplatin-based chemotherapy (FOLFOX) is established as a standard first-line treatment for metastatic colorectal cancer in patients with RAS wild type, showing both safety and efficacy.

Clinical trials, including the updated Calgb/Swog 80405 study, indicate that FOLFOX combined with cetuximab is more effective than chemotherapy with bevacizumab, particularly in left-sided tumors, which represent 70-80% of patients in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cetuximab in association with an oxaliplatin-based chemotherapy as first-line treatment of metastatic colorectal cancer.] Petrelli, F., Ghidini, A., Zaniboni, A.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. [2022]

2. Cyprus pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cetuximab plus FOLFOX in second-line and third-line therapy in metastatic colorectal cancer. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Dose escalating study of cetuximab and 5-FU/folinic acid (FA)/oxaliplatin/irinotecan (FOLFOXIRI) in first line therapy of patients with metastatic colorectal cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Cetuximab plus XELIRI or XELOX for first-line therapy of metastatic colorectal cancer. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of FOLFOX6 and cetuximab in the first-line treatment of patients with metastatic colorectal cancer. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A triplet combination with irinotecan (CPT-11), oxaliplatin (LOHP), continuous infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line treatment in KRAS wt, metastatic colorectal cancer: a pilot phase II trial. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Cetuximab plus capecitabine and irinotecan compared with cetuximab plus capecitabine and oxaliplatin as first-line treatment for patients with metastatic colorectal cancer: AIO KRK-0104--a randomized trial of the German AIO CRC study group. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Seeing the forest through the trees: a systematic review of the safety and efficacy of combination chemotherapies used in the treatment of metastatic colorectal cancer. [2018]

12. Italy pubmed.ncbi.nlm.nih.gov

[Cetuximab in association with an oxaliplatin-based chemotherapy as first-line treatment of metastatic colorectal cancer.] [2018]