What is the mechanism of action of this treatment?

The most common treatments for Head and Neck Cancers include immune checkpoint inhibitors such as PD-1 inhibitors (e.g., Retifanlimab) and PD-L1 inhibitors. These therapies work by blocking the interaction between PD-1 receptors on T-cells and PD-L1 on tumor cells, thereby preventing the tumor from evading the immune system. This reactivates T-cells to recognize and attack cancer cells. This mechanism is particularly important for Head and Neck Cancer patients as it offers a targeted approach to boost the body's immune response against the cancer, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common side effects of treatments for head and neck cancers, particularly those involving PD-1 inhibitors like Retifanlimab, include fatigue, rash, pruritus, diarrhea, and pneumonitis. Severe adverse events can include immune-related effects such as colitis, hepatitis, endocrinopathies, and pneumonitis. Combination therapies often increase the incidence and severity of these side effects, potentially leading to higher rates of severe skin reactions, hypomagnesemia, and sepsis.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA for the treatment of metastatic or recurrent squamous cell carcinoma of the head and neck, particularly for patients with high PD-L1 expression (CPS ≥1). The KEYNOTE-048 trial established its use, either as a monotherapy or in combination with chemotherapy, improving overall survival compared to cetuximab plus chemotherapy. Nivolumab, another PD-1 inhibitor, is also used in this setting, particularly for patients who have progressed on prior chemotherapy.

What other types of research exist?

Promising alternatives to Retifanlimab plus INCAGN02385 and INCAGN02390 for head and neck cancer patients include: 1) Pembrolizumab alone or with chemotherapy (platinum and 5-fluorouracil), which has shown significant efficacy and safety in the KEYNOTE-048 trial. 2) Avelumab, cetuximab, and palbociclib combination, which demonstrated a 42% objective response rate and was well tolerated in a phase I study. 3) Cetuximab combined with platinum and 5-FU, which has shown better tumor response and a low adverse event rate in a systematic review and network meta-analysis.

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PD-L1 Inhibitor

Triple Drug Combo for Head and Neck Cancer

Phase 2

Waitlist Available

Research Sponsored by Incyte Biosciences International Sàrl

Eligibility Criteria Checklist

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

Must have

Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.

ECOG performance status of 0 or 1.

Must not have

Presence of tumors that invade major blood vessels, as shown unequivocally by imaging, and with active bleeding.

Known active CNS metastases and/or carcinomatous meningitis. Participants will be excluded if it has been < 4 weeks since radiation therapy was delivered to the CNS.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 36 months

Awards & highlights

Summary

This trial is testing a new combination of drugs to treat a specific type of head and neck cancer. The treatment includes retifanlimab, which helps the immune system attack cancer, combined with other experimental drugs to enhance this effect. It targets patients whose cancer has come back or spread and who haven't received other treatments yet. Retifanlimab is an immunotherapy drug that helps the immune system attack cancer cells.

Who is the study for?

This trial is for adults with PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck, who haven't had systemic therapy before. They should have a performance status indicating they can care for themselves and not be expected to need curative treatment. Participants must avoid pregnancy, have measurable tumors per specific criteria, provide tissue samples, and not have certain health conditions that could affect their participation.

What is being tested?

The study tests retifanlimab combined with INCAGN02385 and possibly INCAGN02390 against retifanlimab alone in first-line treatment. It aims to find out how safe this combination is and how well it works compared to just using retifanlimab by itself in patients who are new to systemic therapy.

What are the potential side effects?

Potential side effects may include immune-related reactions due to the drugs' action on the immune system, infusion-related responses during drug administration, fatigue from treatment burden, as well as other drug-specific adverse effects which will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

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

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My cancer is in my throat, mouth, or voice box.

Select...

I am fully active or can carry out light work.

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My head or neck cancer can't be treated with the intent to cure, and I haven't refused surgery that could potentially cure a recurrence.

Select...

My tumor is PD-L1 positive with a score of 1% or higher.

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I have not had any drug treatments for my recurrent or metastatic head and neck cancer.

Exclusion Criteria

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

Select...

My tumor is invading major blood vessels and causing active bleeding.

Select...

I do not have active brain metastases or have had brain radiation in the last 4 weeks.

Select...

I haven't had major chest radiation or palliative radiation in the last week.

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My cancer is not in my nasopharynx, sinonasal cavity, or salivary glands.

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My cancer came back or got worse within 6 months after my last treatment.

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I still have side effects from previous treatments that are not mild.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 36 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 36 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 36 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

Progression Free Survival (PFS)

Secondary study objectives

Disease Control Rate (DCR)

Duration of Response (DOR)

Objective Response Rate (ORR)

+2 more

Trial Design

3Treatment groups

Experimental Treatment

Group I: Treatment Group 3: Retifanlimab + INCAGN02385 + INCAGN02390Experimental Treatment3 Interventions

Retifanlimab plus INCAGN02385 and INCAGN02390 will be administered intravenously. Retifanlimab will be administered intravenously every 4 weeks. INCAGN02385 and INCAGN02390 will be administered every 2 weeks.

Group II: Treatment Group 2: Retifanlimab + INCAGN02385Experimental Treatment3 Interventions

Retifanlimab will be administered intravenously every 4 weeks. INCAGN02385 and Placebo for INCAGN02390 will be administered intravenously every 2 weeks.

Group III: Treatment Group 1: Retifanlimab MonotherapyExperimental Treatment2 Interventions

Retifanlimab will be administered intravenously every 4 weeks. Placebos for INCAGN02385 and INCAGN02390 will be administered intravenously every 2 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

INCAGN02385

2018

Completed Phase 1

~30

Retifanlimab

2018

Completed Phase 2

~320

INCAGN02390

2018

Completed Phase 1

~40

Placebo

1995

Completed Phase 3

~2670

0 / 11Eligibility 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 Head and Neck Cancers include immune checkpoint inhibitors such as PD-1 inhibitors (e.g., Retifanlimab) and PD-L1 inhibitors. These therapies work by blocking the interaction between PD-1 receptors on T-cells and PD-L1 on tumor cells, thereby preventing the tumor from evading the immune system. This reactivates T-cells to recognize and attack cancer cells. This mechanism is particularly important for Head and Neck Cancer patients as it offers a targeted approach to boost the body's immune response against the cancer, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Anti-PD-1 and Anti-PD-L1 in Head and Neck Cancer: A Network Meta-Analysis.