What side effects are associated with this type of intervention?

Common treatments for Squamous Cell Carcinoma (SCC), such as chemoradiotherapy (CRT) and platinum-based chemotherapy, have several known side effects. CRT often leads to mucositis, dermatitis, dysphagia, and xerostomia. Platinum-based chemotherapies, like cisplatin, can cause nephrotoxicity, ototoxicity, nausea, vomiting, and myelosuppression. Combining these treatments can intensify these side effects, requiring careful management to ensure patient quality of life.

What prior FDA approvals exist?

The FDA has approved several treatments for Squamous Cell Carcinoma (SCC) of the head and neck, particularly those involving chemoradiotherapy and targeted therapies. Cetuximab, an EGFR inhibitor, has been approved for use in combination with platinum-based chemotherapy and radiation therapy for locally or regionally advanced head and neck SCC. Pembrolizumab, an anti-PD-1 therapy, has also been approved for recurrent or metastatic head and neck SCC, either alone or in combination with chemotherapy. These treatments aim to enhance the efficacy of traditional chemoradiotherapy, similar to the approach being studied with Xevinapant (IAP antagonist) in combination with platinum-based chemotherapy and radiotherapy.

What other types of research exist?

Promising novel alternatives to Xevinapant for Squamous Cell Carcinoma patients include: 1) Immunotherapies such as Pembrolizumab and Nivolumab, which are PD-1 inhibitors showing efficacy in head and neck cancers. 2) Targeted therapies like Cetuximab, an EGFR inhibitor, which has been used in combination with radiation therapy. 3) Novel agents under investigation, such as CXCR4 inhibitors like Plerixafor, which have shown potential in improving radiation treatment outcomes.

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Chemotherapy Agent

Xevinapant + Chemoradiotherapy for Head and Neck Cancer

Q: What is the mechanism of action of this treatment?

The most common treatments for Squamous Cell Carcinoma (SCC) include chemoradiotherapy and targeted therapies. Chemoradiotherapy combines chemotherapy and radiation to damage the DNA of cancer cells, leading to cell death. Targeted therapies, such as Xevinapant (an IAP antagonist), work by inhibiting specific proteins that help cancer cells survive. Xevinapant blocks Inhibitor of Apoptosis Proteins (IAPs), which normally prevent cancer cells from undergoing programmed cell death (apoptosis). By inhibiting IAPs, Xevinapant promotes apoptosis in cancer cells, enhancing the effectiveness of chemoradiotherapy. This is crucial for SCC patients as it can potentially improve treatment outcomes and reduce tumor resistance.

Phase 3

Waitlist Available

Research Sponsored by Debiopharm International SA

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1

For OroPharyngeal Cancer (OPC) participants, primary tumors must be human papillomavirus (HPV)-negative as determined by p16 expression using immunohistochemistry

Must not have

Known allergy to Xevinapant (Debio 1143), cisplatin, carboplatin, other platinum-based agent or any excipient known to be present in any of these products or in the placebo formulation

Prior definitive or adjuvant Radiotherapy (RT) and/or radical surgery to the head and neck region which may jeopardize the primary tumor irradiation plan, or any other prior SCCHN systemic treatment, including investigational agents

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new drug called Xevinapant to see if it can help improve the effectiveness of standard cancer treatments in patients with advanced head and neck cancer. The drug works by making the cancer cells more sensitive to chemotherapy and radiation.

Who is the study for?

This trial is for adults with untreated locally advanced squamous cell carcinoma of the head and neck (stages III, IVa, or IVb), specifically not from nasopharynx or oral cavity origins. Participants must have good performance status (ECOG PS 0 or 1), manageable peripheral neuropathy (< grade 2), non-HPV related tumors for those with oropharyngeal cancer, and adequate organ function. Those with allergies to study drugs, metastatic disease, significant recent weight loss without nutritional support, low albumin levels, prior head/neck radiation or surgery that affects treatment area are excluded.

What is being tested?

The TrilynX study tests whether adding Xevinapant (Debio 1143) to standard chemoradiotherapy improves outcomes in patients with locally advanced squamous cell carcinoma of the head and neck. Patients will receive either Xevinapant plus cisplatin chemotherapy and intensity-modulated radiotherapy (IMRT) or a placebo alongside the same chemo-radiotherapy regimen.

What are the potential side effects?

Potential side effects include reactions typical of chemotherapy like nausea, vomiting, hair loss; radiotherapy such as skin irritation and dry mouth; plus any specific effects from Xevinapant which could involve changes in blood counts leading to increased infection risk among others.

Eligibility Criteria

Inclusion Criteria

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

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I am fully active or can carry out light work.

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My oropharyngeal cancer is not caused by HPV.

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I have a specific type of throat cancer that has not been treated yet.

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My nerve damage does not severely affect my daily activities.

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My cancer can be measured by scans according to specific criteria.

Exclusion Criteria

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

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I am allergic to Xevinapant, cisplatin, carboplatin, or similar drugs.

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I have had surgery or radiation in the head/neck that affects current treatment plans.

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My cancer has spread to other parts of my body (stage IV).

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My cancer originates in the head or neck region.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Event-Free Survival (EFS)

Secondary study objectives

Changes from Baseline in Global Health Status/Quality of Life (GHS/QoL) and Fatigue Symptom

Changes from Baseline in Swallowing and Pain Symptoms

Complete Response Rate (CRR)

+4 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Xevinapant (Debio 1143)Experimental Treatment3 Interventions

Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Xevinapant (Debio 1143) Monotherapy period (Cycles 4-6): • Xevinapant (Debio 1143)

Group II: PlaceboActive Control3 Interventions

Participants will receive: Concomitant chemo-radiation therapy period (Cycles 1-3): * Radiotherapy * Cisplatin * Matched placebo Monotherapy period (Cycles 4-6): • Matched placebo

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

DEBIO-1143

Not yet FDA approved

Cisplatin

2013

Completed Phase 3

~3120

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

The most common treatments for Squamous Cell Carcinoma (SCC) include chemoradiotherapy and targeted therapies. Chemoradiotherapy combines chemotherapy and radiation to damage the DNA of cancer cells, leading to cell death. Targeted therapies, such as Xevinapant (an IAP antagonist), work by inhibiting specific proteins that help cancer cells survive. Xevinapant blocks Inhibitor of Apoptosis Proteins (IAPs), which normally prevent cancer cells from undergoing programmed cell death (apoptosis). By inhibiting IAPs, Xevinapant promotes apoptosis in cancer cells, enhancing the effectiveness of chemoradiotherapy. This is crucial for SCC patients as it can potentially improve treatment outcomes and reduce tumor resistance.

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