Amivantamab for Esophageal Cancer
Recruiting in Palo Alto (17 mi)
+9 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must not be taking: Chemotherapy, Targeted therapy
Disqualifiers: Active malignancy, Hepatitis B, Hepatitis C, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
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.12345
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
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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
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Trial 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 (Monoclonal Antibodies)
Trial OverviewResearchers 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
1Treatment groups
Experimental Treatment
Group I: AmivantamabExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Monmouth (Limited protocol activities)Middletown, NJ
Memorial Sloan Kettering Commack (Limited Protocol Activities)Commack, NY
University of California, IrvineIrvine, CA
Massachusetts General Hospital (Data Collection Only)Boston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
Janssen PharmaceuticalsIndustry Sponsor
References
Nivolumab for the treatment of esophageal cancer. [2022]Introduction: Esophageal cancer (EC) is the seventh most common cancer and the sixth leading cause of cancer death worldwide. The prognosis for advanced EC patients remains poor and there are few effective therapeutic agents available. Nivolumab is a fully human IgG4 monoclonal antibody that exerts antitumor activity by inhibiting the interaction of programmed cell death protein 1 on activated lymphocytes with its ligands. Nivolumab monotherapy showed significant benefit for overall survival of patients with advanced esophageal squamous cell carcinoma (ESCC) relative to taxane as a second-line treatment. Additionally, adjuvant nivolumab monotherapy showed significant disease-free survival benefit relative to placebo for resectable EC patients with residual pathologic disease who had received neoadjuvant chemoradiotherapy followed by surgery.Areas covered: Here, we provide an overview of checkpoint blockade with nivolumab and present the available clinical data related to its use in EC.Expert opinion: Nivolumab should be the standard second-line treatment for advanced ESCC patients and possibly adjuvant treatment of choice after neoadjuvant chemoradiotherapy followed by surgery. Trials assessing efficacy of a combination of cytotoxic agents and nivolumab as first-line treatment, nivolumab-containing chemoradiotherapy, and neoadjuvant chemotherapy are ongoing. These trials should result in improved protocols for better clinical outcomes in EC.
MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma. [2021]Standard-of-care, first-line therapy for patients with advanced HER2+ gastric/gastroesophageal junction adenocarcinoma is chemotherapy plus trastuzumab, a monoclonal antibody (mAb) targeting HER2. Margetuximab is an Fc-optimized mAb that binds HER2. Retifanlimab, a humanized IgG4 mAb, binds to PD-1 and blocks its interaction with PD-L1/2. Tebotelimab, an IgG4κ bispecific DART® molecule, binds PD-1 and lymphocyte activation gene 3 concomitantly, disrupting these nonredundant inhibitory pathways to further restore exhausted T-cell function. Here, we describe the design and rationale of the randomized, open-label, Phase II/III MAHOGANY trial evaluating margetuximab plus retifanlimab with/without chemotherapy and margetuximab plus tebotelimab with chemotherapy in first-line unresectable metastatic/locally advanced gastroesophageal junction adenocarcinoma. Primary end points include objective response rate, overall survival and safety/tolerability. Clinical trial registration: NCT04082364 (ClinicalTrials.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]Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers.
The effectivity of targeted therapy and immunotherapy in patients with advanced metastatic and non-metastatic cancer of the esophagus and esophago-gastric junction. [2023]Therapies that target specific tumor drivers or immune checkpoints are increasingly explored for esophageal cancer patients. This review addresses developments in therapies with targeted anti-human epidermal growth factor receptor 2 (HER2) agents and immune checkpoint inhibitors in patients with stage IV esophageal cancer. First-line palliative treatment with the anti-HER2 agent trastuzumab in combination with chemotherapy has been approved for use in patients with HER2 positive gastro-esophageal adenocarcinoma. Neoadjuvant chemoradiotherapy plus perioperative trastuzumab however has not demonstrated a survival benefit in advanced esophageal cancer patients eligible for surgery. Potentially better responses are expected with dual agent anti-HER2 therapy instead of monotherapy. In the metastatic setting, the antibody-drug conjugate trastuzumab deruxtecan is effective after progression on trastuzumab. Nivolumab and pembrolizumab, antibodies blocking the programmed cell death 1 (PD-1) receptor on T cells, have recently gained approval for clinical use in esophageal cancer patients for specific indications. Synergistic effects might be achieved with combinations of immune checkpoint inhibitors that target PD-1 on T cells or PD ligand 1 (PD-L1) on tumor cells and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) receptor on T cells. Multiple clinical trials investigating combinations of targeted and immunotherapies, with or without (neo)adjuvant chemo(radio)therapy, for curative and palliative treatment, are underway, and are expected to deliver a long-awaited improvement in the prognosis of esophageal cancer patients.
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]The addition of nivolumab to chemotherapy improves survival in patients with advanced oesophagogastric (oesophageal, gastric, or gastro-oesophageal junction) adenocarcinoma; however, outcomes remain poor. We assessed the safety and activity of regorafenib in combination with nivolumab and chemotherapy in the first-line treatment of advanced oesophagogastric adenocarcinoma.