Amivantamab + Chemotherapy vs Cetuximab + Chemotherapy for Colorectal Cancer (OrigAMI-2 Trial)
Recruiting in Palo Alto (17 mi)
+136 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Janssen Research & Development, LLC
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
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) when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6) or 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus cetuximab and mFOLFOX6 or FOLFIRI in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS)/ Neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) wild type (WT) unresectable or metastatic left-sided colorectal cancer.
Is the drug Amivantamab or Cetuximab a promising treatment for colorectal cancer?Cetuximab is a promising drug for colorectal cancer. It works well with chemotherapy, improving response rates and survival in patients. It can also help patients who didn't respond to other treatments before.145810
What safety data is available for Amivantamab and Cetuximab in colorectal cancer treatment?The safety data for Cetuximab (Erbitux) in colorectal cancer treatment is well-documented. Post-marketing surveillance in Japan has been conducted to verify its safety in practical use. Clinical trials have shown that Cetuximab is generally well tolerated, with common toxicities including acne-form rash and hypomagnesemia. The severity of skin toxicity has been correlated with response and survival rates. Grade 3 toxicities are rare, with skin toxicity at 8%, diarrhea at 10%, nausea at 3%, vomiting at 3%, and fatigue at 8%. There is no specific safety data provided for Amivantamab in the provided research.246710
What data supports the idea that Amivantamab + Chemotherapy vs Cetuximab + Chemotherapy for Colorectal Cancer is an effective drug?The available research shows that Cetuximab combined with chemotherapy has been effective in treating colorectal cancer, especially in patients who have already tried other treatments. For example, one study found that using Cetuximab with irinotecan helped patients who had not responded to previous treatments, with a 20% response rate and a median survival of 10.4 months. Another study showed that adding Cetuximab to chemotherapy improved the time patients lived without the cancer getting worse and increased the chances of surgery to remove the cancer. However, there is no specific data provided on Amivantamab combined with chemotherapy for colorectal cancer, so we cannot compare its effectiveness directly to Cetuximab in this context.23459
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that participants with known allergies or hypersensitivity to the trial drugs are excluded, so you should discuss your current medications with the trial team.
Eligibility Criteria
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
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.
My left-sided colorectal cancer is confirmed and cannot be surgically removed.
My tumor is KRAS, NRAS, and BRAF wild-type.
Exclusion Criteria
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.
My cancer is HER2-positive and has dMMR/MSI-H status.
I have been treated with drugs targeting EGFR or MET before.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A: Amivantamab in Combination With ChemotherapyExperimental Treatment5 Interventions
Participants will receive amivantamab in combination with chemotherapy (mFOLFOX6 \[chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and oxaliplatin\] or FOLFIRI \[chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride\]) 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 in Combination With ChemotherapyActive Control5 Interventions
Participants will receive cetuximab in combination with chemotherapy (mFOLFOX6 or FOLFIRI) for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.
Amivantamab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Rybrevant for:
- Locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
- Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations
🇪🇺 Approved in European Union as Rybrevant for:
- Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations
- Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Grady Memorial HospitalAtlanta, GA
Winship Cancer Institute Emory UniversityAtlanta, GA
Fort Wayne Medical Oncology & HematologyFort Wayne, IN
Rutgers Cancer InstituteNew Brunswick, NJ
More Trial Locations
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Who is running the clinical trial?
Janssen Research & Development, LLCLead Sponsor
References
[Which role do new therapeutic options play in palliative care of colorectal cancer?]. [2018]Therapeutic options in the treatment of metastatic colorectal cancer have recently been expanded by the introduction of two new monoclonal antibodies: bevacizumab and cetuximab. These antibodies were the proof of principle of two exciting new antitumor strategies: antiangiogenesis and inhibition of epidermal growth factor (EGF) receptor. Bevacizumab binds to vascular endothelial growth factor and thus blocks its angiogenic effects. In a randomized phase III trial bevacizumab in combination with irinotecan + 5-fluorouracil/leucovorin (IFL) was compared to chemotherapy alone as first-line treatment. The combination showed a superior response rate, a prolonged progression-free and overall survival. Cetuximab binds to the EGF receptor and thus inhibits its activation by its natural ligand. In a randomized phase II trial irinotecan refractory patients were treated with cetuximab alone or cetuximab plus irinotecan. The combination showed a response rate of 22,5% and a prolonged progression-free survival identifying cetuximab as an important new option for this patient group.
Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. [2019]Cetuximab (Erbitux) has shown activity in patients with metastatic colorectal cancer (mCRC). To evaluate the cost-effectiveness of this drug combined with irinotecan in mCRC, a model-based cost-effectiveness analysis (CEA) was performed. Data on cetuximab obtained from Medline in December 2004 and from the 2004 ASCO-meeting were analyzed for life years gained (LYG) with regard to the use of this monoclonal antibody (MAb). Norwegian prices as of January 2005 were employed. The LYG ranged between 1.7 and 2.0 years. The median cost per patient treated was calculated to 34,256 Euro to 45,764 Euro yielding a cost per LYG in the range between 205,536 Euro and 323,040 Euro. Sensitivity analysis documented price of cetuximab and survival gain to be the major factors influencing the cost-effectiveness ratio. In conclusion, the analysis indicates cetuximab to be a promising, but very expensive antibody.
Cetuximab in colon cancer. [2018]In the last decade remarkable progress has been made in the treatment of metastatic colorectal cancer due to the introduction of oxaliplatin and irinotecan in clinical practice. The addition of biological agents seems to offer a chance to further enhance the activity of conventional chemotherapy. Cetuximab, a chimeric mouse-human monoclonal antibody targeting the extracellular domain of the epidermal growth factor receptor (EGFR), has shown low but detectable activity when employed in pretreated patients either as a single agent or in combination with irinotecan. Cetuximab in combination with irinotecan has been registered in the USA and Europe for the treatment of patients with metastatic colorectal cancer expressing the EGFR after failure of prior irinotecan-based cytotoxic therapy. The role of cetuximab in first-line therapy is still investigational. Some phase II trials assessing cetuximab plus chemotherapy demonstrated a high objective response rate and promising results in terms of time to progression and overall survival; data from phase III trials are pending. Further studies are needed to investigate the efficacy of cetuximab in combination with conventional chemotherapy in the adjuvant/neoadjuvant setting and to define criteria for a better selection of patients for this type of treatment.
Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. [2018]Cetuximab (Erbitux) in combination with irinotecan is the most promising combination in heavily pretreated patients with advanced colorectal cancer. Efficacy of this combination was confirmed in the pivotal BOND I study. The aim of the present study was to evaluate efficacy and toxicity of a combination regimen of cetuximab and irinotecan but in contrast to the BOND I study all patients had previously received 5-FU, oxaliplatin and irinotecan and all had progressed during or shortly after completion of treatment. Before January 2005 salvage therapy with cetuximab and irinotecan was not used in Denmark. The Danish government had initiated a national programme for patients with advanced cancer and according to this programme the National Board of Health may approve and finance experimental treatment. From January 2005 to September 2005, 65 consecutive patients were treated with cetuximab (weekly) and irinotecan (each 2 or 3 weeks) at three university hospitals. Median age was 57 years (23-78), and median performance status was 1 (0-3). Response rate was 20%, median TTP was 5.5 months and median OS was 10.4 months. Response and survival was significantly correlated with severity of skin toxicity. Toxicity grade 3 was rare (skin toxicity 8%, diarrhoea 10%, nausea 3%, vomiting 3%, fatigue 8%). Salvage therapy with cetuximab and irinotecan is effective in patients pretreated with irinotecan, and oxaliplatin and in a general population the results from the BOND I study was confirmed.
Cetuximab plus XELIRI or XELOX for first-line therapy of metastatic colorectal cancer. [2018]Modern chemotherapy combinations for metastatic colorectal cancer (mCRC) comprise infusional 5-fluorouracil (5-FU), leucovorin, and irinotecan or oxaliplatin. The fluoropyrimidine derivative capecitabine is at least as effective as 5-FU plus leucovorin bolus regimens. It displays a favorable toxicity profile and offers the advantages of oral administration. The epidermal growth factor receptor antibody cetuximab induces synergistic antitumor activity when combined with chemotherapy. In pretreated patients, cetuximab can restore the sensitivity to irinotecan and, therefore, has been registered in this setting. Several phase I/II trials have investigated the combination of cetuximab with irinotecan-based or oxaliplatin-based chemotherapy for the first-line treatment of mCRC. These combinations have been proven to be safe and have provided promising efficacy data. A recent phase III trial confirmed improved progression-free survival, response rates, and a particularly significant increase of secondary resection rates for the combination of FOLFIRI (infusional 5-FU/leucovorin/irinotecan) plus cetuximab compared with FOLFIRI alone. In this review, we discuss the background of combining XELIRI (capecitabine/irinotecan) or XELOX (capecit-abine/oxaliplatin) with cetuximab for the first-line treatment of mCRC and present available data of these combined cytotoxic and targeted treatment approaches.
Cetuximab in the management of colorectal cancer. [2023]Cetuximab, a chimeric IgG1 monoclonal antibody that targets the ligand-binding domain of the epidermal growth factor receptor (EGFR), is active in metastatic colorectal cancer (mCRC). As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. More recent studies show promising activity in second-line treatment after oxaliplatin-based therapy failure, and with first-line chemotherapy, where increased response rates seen with adding cetuximab to first-line therapy for mCRC may increase chances for curative surgery in a population for whom the therapy goal would otherwise be palliative. Cetuximab is generally well tolerated; common toxicities are acne-form rash and hypomagnesemia. Rash intensity is associated with clinical efficacy, and in the future, may be used as a marker for optimal drug exposure. Cetuximab activity in mCRC is not correlated with EGFR expression, and consequently other markers will be needed to identify the most likely responders. Cetuximab has clinically emerged as a core agent, along with 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab, for overall mCRC management to optimize survival. Ongoing studies are exploring best combinations of cetuximab with these other agents to maximize patient outcome.
A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]Cetuximab (Erbitux(®)) was approved for the treatment of metastatic colorectal cancer in Japan in 2008. To verify information on the safety in practical use of cetuximab, we conducted post-marketing surveillance in accordance with the conditions for approval.
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. [2022]AIO KRK-0104 investigated first-line therapy of metastatic colorectal cancer (mCRC) with cetuximab, capecitabine and irinotecan versus cetuximab, capecitabine and oxaliplatin. This analysis investigated the impact of primary tumor location on outcome of patients.
Cetuximab in colon cancer. [2022]In the last decade remarkable progress has been made in the treatment of metastatic colorectal cancer due to the introduction of oxaliplatin and irinotecan in clinical practice. The addition of biological agents seems to offer a chance to further enhance the activity of conventional chemotherapy. Cetuximab, a chimeric mouse-human monoclonal antibody targeting the extracellular domain of the epidermal growth factor receptor (EGFR), has shown low but detectable activity when employed in pretreated patients either as a single agent or in combination with irinotecan. Cetuximab in combination with irinotecan has been registered in the USA and Europe for the treatment of patients with metastatic colorectal cancer expressing the EGFR after failure of prior irinotecan-based cytotoxic therapy. The role of cetuximab in first-line therapy is still investigational. Some phase II trials assessing cetuximab plus chemotherapy demonstrated a high objective response rate and promising results in terms of time to progression and overall survival; data from phase III trials are pending. Further studies are needed to investigate the efficacy of cetuximab in combination with conventional chemotherapy in the adjuvant/neoadjuvant setting and to define criteria for a better selection of patients for this type of treatment.
Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. [2020]Combination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients' selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1. Interestingly, the high-affinity FcγRIIIa V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity.