Amivantamab for Esophageal Cancer

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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a drug called amivantamab to see if it can treat esophagogastric cancer with specific genetic changes. The drug works by blocking proteins that help cancer cells grow. Researchers also want to know if the drug is safe and causes only mild side effects.

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.

What makes the drug Amivantamab unique for treating esophageal cancer?

Amivantamab is unique because it is a bispecific antibody that targets both EGFR (epidermal growth factor receptor) and MET (a receptor involved in cell growth and survival), which may offer a novel approach compared to existing treatments that typically target only one pathway. This dual targeting could potentially provide a more effective treatment option for esophageal cancer, especially in cases where other therapies have limited efficacy. ^{1 2 3 4 5}

Research Team

Steven Maron, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 Business School

John (Jack) Lawrence

Janssen Pharmaceuticals

Chief Medical Officer since 2023

MD from University of Virginia School of Medicine

Findings from Research

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Nivolumab for the treatment of esophageal cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma. [2021]

3. England 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. [2023]

4. Italy 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. [2023]

5. England 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. [2023]