Amivantamab for Esophageal Cancer

Not currently recruiting at 9 trial locations

Overseen By Yelena Janjigian, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Chemotherapy, Targeted therapy

Disqualifiers: Active malignancy, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether amivantamab, a targeted therapy, effectively and safely treats esophagogastric cancer with specific genetic changes known as EGFR or MET amplification. Researchers aim to determine if the drug can slow or stop cancer growth in patients who have already tried other treatments. Suitable candidates for this trial include those with esophagogastric cancer unresponsive to previous treatments and identified with these genetic changes. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing early access to potentially effective therapy.

Will I have to stop taking my current medications?

The trial requires that you have not received chemotherapy, targeted therapy, or biological therapy within 2 weeks before starting the study. If you are on these treatments, you may need to stop them before joining the trial.

Is there any evidence suggesting that amivantamab is likely to be safe for humans?

Research has shown that amivantamab has undergone safety testing in other studies. For example, one study found that serious side effects occurred in about 27.3% of patients, indicating that most patients experienced either mild side effects or none at all.

Amivantamab is also used to treat other cancers, such as non-small cell lung cancer, demonstrating prior human testing.

Overall, while some serious side effects can occur, most people experience milder ones. The advanced stage of this trial suggests the treatment is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Amivantamab is unique because it targets specific proteins on cancer cells, known as EGFR and MET, which are often involved in the growth of esophageal cancer. Unlike traditional chemotherapy that attacks rapidly dividing cells in general, amivantamab specifically binds to these proteins, potentially reducing damage to healthy cells and improving treatment precision. Researchers are excited about this approach because it may offer a more targeted therapy with the potential for better outcomes and fewer side effects compared to the current standard treatments like chemotherapy and radiation.

What evidence suggests that amivantamab might be an effective treatment for esophagogastric cancer?

Research has shown that amivantamab is a promising treatment for certain cancers, particularly those with EGFR and MET mutations. In a recent study, patients with these mutations responded well to the drug. Amivantamab targets and blocks these specific mutations, which often promote cancer growth. Previous studies have demonstrated that amivantamab can improve survival when combined with chemotherapy in lung cancer. This trial will assess its effectiveness for esophageal cancer patients with similar genetic markers. ^{1 3 6 7 8}

Who Is on the Research Team?

Steven Maron, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with esophagogastric cancer that's spread or can't be removed surgically, who've tried at least one treatment before. They must have specific genetic changes (EGFR or MET amplification) and measurable disease. People with certain heart conditions, other active cancers, uncontrolled illnesses, recent blood clots, liver diseases including hepatitis B or C, lung conditions like ILD, mental health issues affecting trial participation are excluded.

Inclusion Criteria

I have not taken EGFR or MET inhibitors for my esophagogastric cancer.

My blood counts and liver/kidney functions are within normal ranges.

Subject or legally authorized representative is willing and able to provide written informed consent

Exclusion Criteria

I have no progressing cancer except for certain skin cancers or treated cervical cancer.

I do not have any major health issues that could interfere with the trial.

Pregnancy, breastfeeding, or planning to conceive during trial duration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amivantamab intravenously weekly for the first cycle, and biweekly subsequently, continuing for up to 2 years or until disease progression or other discontinuation criteria are met

Up to 2 years

Weekly visits for the first cycle, biweekly visits thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab

Trial Overview

Researchers are testing amivantamab to see if it's effective and safe in treating esophagogastric cancer with EGFR or MET gene amplifications. Participants will have had previous treatments and their response to this new drug will be closely monitored.

How Is the Trial Designed?

Group I: Amivantamab Experimental Treatment 1 Intervention

Patients will receive amivantamab intravenously weekly for the first cycle, and biweekly subsequently at a dose of 1050mg (patients \<80kg) or 1400mg (patients ≥80kg). The initial dose will be administered over 2 days in split doses in order to mitigate the risk of infusion reactions. Therapy will continue for up to 2 years or until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reason to discontinue treatment occurs-whichever comes first.

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

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

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

Published Research Related to This Trial

In a randomized phase II trial involving 87 patients with metastatic esophageal or gastroesophageal junction cancers, the combination of paclitaxel and cixutumumab did not show a significant improvement in progression-free survival compared to paclitaxel alone, with median PFS of 2.6 months versus 2.3 months, respectively.

Both treatment arms were well tolerated, but the addition of cixutumumab did not enhance overall survival, which was 6.7 months for paclitaxel alone and 7.2 months for the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial. Stockton, S., Catalano, P., Cohen, SJ., et al.[2023]

Nivolumab, a monoclonal antibody that inhibits programmed cell death protein 1, has shown significant benefits in overall survival for patients with advanced esophageal squamous cell carcinoma (ESCC) when used as a second-line treatment compared to taxane.

Adjuvant nivolumab therapy after neoadjuvant chemoradiotherapy and surgery has demonstrated a significant improvement in disease-free survival for resectable esophageal cancer patients with residual disease, suggesting it could be a standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for the treatment of esophageal cancer. Mikuni, H., Yamamoto, S., Kato, K.[2022]

The MAHOGANY trial is a Phase II/III study designed to evaluate the effectiveness and safety of margetuximab combined with either retifanlimab or tebotelimab, with or without chemotherapy, in treating advanced HER2+ gastric and gastroesophageal junction adenocarcinoma.

The primary endpoints of the trial include objective response rate and overall survival, which will help determine the efficacy of these combinations in improving treatment outcomes for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma. Catenacci, DV., Rosales, M., Chung, HC., et al.[2021]

In a phase 2 trial involving 39 patients with advanced HER2-negative oesophagogastric adenocarcinoma, the combination of regorafenib, nivolumab, and chemotherapy resulted in 71% of patients being progression-free at 6 months, indicating promising efficacy.

The treatment was generally safe, with the most common adverse effects being fatigue and decreased neutrophil count, and no treatment-related deaths reported, suggesting that this combination could be a viable option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: a single-arm, single-centre, phase 2 trial. Cytryn, SL., Moy, RH., Cowzer, D., et al.[2023]

Trastuzumab, an anti-HER2 agent, is approved for first-line treatment in HER2 positive gastro-esophageal adenocarcinoma, showing effectiveness when combined with chemotherapy, but not with neoadjuvant chemoradiotherapy for advanced cases.

Immune checkpoint inhibitors like nivolumab and pembrolizumab have been approved for specific uses in esophageal cancer, and combining these with other therapies may enhance treatment outcomes, with ongoing clinical trials exploring these combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectivity of targeted therapy and immunotherapy in patients with advanced metastatic and non-metastatic cancer of the esophagus and esophago-gastric junction. Valkema, MJ., Mostert, B., Lagarde, SM., et al.[2023]

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Amivantamab (JNJ-61186372), an anti-EGFR-MET ...

Amivantamab (JNJ-61186372) is a novel, fully human anti-EGFR-MET bispecific antibody whose mechanism of action can target both EGFR- and MET-driven disease and ...

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The purpose of this expanded access program (EAP) is to provide amivantamab for the treatment of participants with metastatic non-small cell lung cancer who ...

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Additionally, investigators reported that the experimental regimen demonstrated a safety profile that was consistent with previous reports for ...