What side effects are associated with this type of intervention?

Common treatments for Head and Neck Squamous Cell Carcinoma (HNSCC) that target EGFR, such as cetuximab, often result in side effects like skin rash, fatigue, muscle cramps, and infusion-related reactions. When combined with chemotherapy agents like cisplatin or paclitaxel, additional side effects can include severe hypomagnesemia, severe skin reactions, and sepsis. Amivantamab, a bispecific antibody targeting EGFR and MET receptors, is being studied for its safety and efficacy, and its side effect profile may include similar adverse events.

What prior FDA approvals exist?

The FDA has approved several treatments for Head and Neck Squamous Cell Carcinoma (HNSCC). Pembrolizumab, an immune checkpoint inhibitor targeting PD-1, has been approved for use in patients with recurrent or metastatic HNSCC, particularly those expressing high levels of PD-L1. Additionally, cetuximab, an EGFR inhibitor, has been approved for use in combination with platinum-based chemotherapy and as a monotherapy for patients with recurrent or metastatic HNSCC. These treatments are somewhat similar to amivantamab, which targets both EGFR and MET receptors, and is currently being studied for its safety and efficacy in HNSCC.

What other types of research exist?

Promising novel alternatives to Amivantamab for HNSCC patients include: 1) Pembrolizumab (a PD-1 inhibitor) which has shown efficacy in combination with chemotherapy, 2) Cetuximab (an EGFR inhibitor) which can be used alone or in combination with other agents, and 3) Investigational agents like Palbociclib (a CDK4/6 inhibitor) in combination with Cetuximab. These alternatives have shown potential in clinical trials and may offer effective treatment options in 2024.

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Monoclonal Antibodies

Amivantamab Combinations for Head and Neck Cancer (OrigAMI-4 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adequate organ and bone marrow function without recent transfusions or use of granulocyte colony-stimulating factor

Negative p16 status for all participants with an oropharyngeal tumor

Must not have

Untreated brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation

Uncontrolled illness including non-infectious interstitial lung disease (ILD)/pneumonitis/pulmonary fibrosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years and 2 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called amivantamab alone and with two other drugs, pembrolizumab and paclitaxel. It targets patients with head and neck cancer that has come back or spread. Amivantamab blocks signals that help cancer grow, pembrolizumab helps the immune system fight cancer, and paclitaxel stops cancer cells from dividing. Pembrolizumab has shown benefits when used with chemotherapy.

Who is the study for?

This trial is for people with recurrent or metastatic head and neck cancer, including squamous cell carcinoma. Participants should have a type of cancer that has returned after treatment or spread to other parts of the body.

What is being tested?

The study tests amivantamab alone, combined with pembrolizumab, and in combination with paclitaxel. It aims to find out how safe these treatments are and how well they work against advanced head and neck cancer.

What are the potential side effects?

Possible side effects include allergic reactions to medication, fatigue, nausea, skin rash, infusion-related reactions from amivantamab or pembrolizumab, and hair loss or nerve damage from paclitaxel.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My organs and bone marrow are functioning well without recent medical help.

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My oropharyngeal tumor is p16 negative.

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I can carry out all my daily activities without help.

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My cancer originates in the throat, mouth, or voice box.

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My cancer is a type of head and neck cancer that has returned or spread and cannot be cured with surgery or radiation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have brain metastases or spinal issues not treated by surgery or radiation.

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I do not have any uncontrolled illnesses like lung scarring or inflammation.

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I have a history of serious heart problems.

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I received radiotherapy for symptom relief within the last week.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years and 2 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years and 2 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years and 2 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cohort 3A: Number of Participants With Dose-limiting Toxicities (DLT)

Cohort 3A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Severity

Cohorts 1, 2, 3B and 4: Objective Response Rate

Secondary study objectives

Cohort 1 and 4: Accumulation Ratio (R) of Amivantamab

Cohort 1 and 4: Area Under the Curve From Time Zero to tau (AUC[0-tau]) of Amivantamab

Cohort 1 and 4: Area Under the Serum Concentration Curve Verses Time Curve From Time t1 to t2 (AUC[t1-t2]) of Amivantamab

+8 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Cohort 4: Amivantamab MonotherapyExperimental Treatment1 Intervention

Participants will receive subcutaneous injection of amivantamab monotherapy 1600 mg (2240 mg, if body weight \>=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight \>=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards.

Group II: Cohort 3B (Dose Expansion): Amivantamab + PaclitaxelExperimental Treatment2 Interventions

Participants will receive subcutaneous injection of amivantamab at the determined RP2CD in addition to intravenous injection of paclitaxel 175 mg/m\^2 q3w (on Day 1 of each 21-day cycle) as confirmed by SET in Cohort 3A.

Group III: Cohort 3A (Dose Confirmation): Amivantamab + PaclitaxelExperimental Treatment2 Interventions

Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight \>=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight \>=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of paclitaxel 175 mg/m\^2 q3w (on Day 1 of each 21-day cycle) in dose confirmation Cohort 3A. The recommended Phase 2 combination dose (RP2CD) of amivantamab will be determined in conjunction with study evaluation team (SET) in this dose confirmation Cohort 3A.

Group IV: Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in)Experimental Treatment2 Interventions

Group V: Cohort 1: Amivantamab Monotherapy (Dose Expansion)Experimental Treatment1 Intervention

Participants will receive subcutaneous injection of amivantamab monotherapy 1600 milligrams (mg) (2240 mg, if body weight \>=80 kilograms \[kg\]) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight \>=80 kg) once every week (q1w) for the remainder of Cycle 1 (Days 8 and 15), and every 3 weeks (q3w) from Cycle 2 onwards.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Paclitaxel

2011

Completed Phase 4

~5450

Pembrolizumab

2017

Completed Phase 3

~3130

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Head and Neck Squamous Cell Carcinoma (HNSCC) include targeted therapies, immunotherapies, and chemotherapies. Targeted therapies, such as amivantamab, work by inhibiting specific proteins like EGFR and MET that are involved in tumor growth and survival. This is crucial for HNSCC patients as these receptors are often overexpressed, leading to aggressive tumor behavior. Immunotherapies, like pembrolizumab, enhance the body's immune response against cancer cells by targeting immune checkpoints such as PD-1/PD-L1. Chemotherapies, including agents like paclitaxel, disrupt cell division, leading to cancer cell death. Understanding these mechanisms helps in selecting the most effective treatment strategy, potentially improving outcomes and reducing side effects for HNSCC patients.

In vitro effect of radiation, antibody to epidermal growth factor receptor and Docetaxel in human head and neck squamous carcinoma cells with mutant P53 and over-expressed EGFR.