Triple Drug Combo for Head and Neck Cancer

Not currently recruiting at 119 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Incyte Biosciences International Sàrl

Must not be taking: Checkpoint inhibitors

Disqualifiers: Nasopharynx tumors, CNS metastases, 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

Compensation: Varies

Number of Visits: 4

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new triple-drug combination for treating squamous cell carcinoma, a specific type of head and neck cancer. Researchers aim to determine if adding two new drugs, INCAGN02385 and INCAGN02390, to the existing drug retifanlimab (Zynyz) benefits patients more than using retifanlimab alone. The trial seeks participants with head and neck cancer that has recurred or spread and who have not yet received systemic treatment. Participants should have PD-L1-positive tumors, indicating the presence of a protein that may predict their response to these treatments. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had any anticancer therapies or participated in another clinical study within 21 days before starting this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that retifanlimab is generally safe for people. In earlier studies, patients tolerated it well, and it maintained a good safety record. The treatment was considered acceptable, with manageable side effects.

For the combination of retifanlimab with INCAGN02385, early results suggest it is also safe. Initial studies showed that patients did not experience severe side effects. This combination has been tested in other trials, and the safety results are encouraging.

The triple combination of retifanlimab, INCAGN02385, and INCAGN02390 has also undergone study. Early safety results indicate that this combination is tolerable, with no major safety issues for patients.

Overall, the available data suggests these treatments are safe, but each person's experience may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they offer a novel approach compared to existing therapies. While most current treatments focus on surgery, radiation, and chemotherapy, the new drugs—Retifanlimab, INCAGN02385, and INCAGN02390—operate by enhancing the immune system's ability to fight cancer. Retifanlimab, a PD-1 inhibitor, helps block a pathway that tumors use to evade the immune system. INCAGN02385 and INCAGN02390 are designed to work alongside Retifanlimab, potentially boosting its effectiveness. This triple drug combo could lead to more effective and targeted cancer treatment options, offering hope for better outcomes in patients.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that retifanlimab can significantly slow tumor growth in patients with head and neck squamous cell carcinoma. In this trial, participants will join different treatment groups to evaluate the effectiveness of various combinations.

One group will receive retifanlimab alone, which studies indicate reduces the risk of cancer progression or death. Another group will receive a combination of retifanlimab with INCAGN02385, which early results suggest is safe and may enhance the immune system's ability to fight cancer. A third group will receive retifanlimab combined with both INCAGN02385 and INCAGN02390. Adding INCAGN02390 aims to block more pathways that cancer cells use to evade the immune system. Initial studies on INCAGN02390 alone showed it is well-tolerated, suggesting it could safely enhance the effectiveness of the other drugs. These combinations are being explored as potential first-choice treatments for head and neck cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Matthias Bartenstein, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

I am fully active or can carry out light work.

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.

Exclusion Criteria

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

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

Less than 3-month life expectancy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive retifanlimab, INCAGN02385, and INCAGN02390 as first-line treatment for PD-L1-positive recurrent/metastatic squamous cell carcinoma of the head and neck

24 months

Retifanlimab every 4 weeks, INCAGN02385 and INCAGN02390 every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• INCAGN02385
• INCAGN02390
• Placebo
• Retifanlimab

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment Group 3: Retifanlimab + INCAGN02385 + INCAGN02390 Experimental Treatment 3 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 + INCAGN02385 Experimental Treatment 3 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 Monotherapy Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Incyte Biosciences International Sàrl

Lead Sponsor

Trials

16

Recruited

810+

Published Research Related to This Trial

Duligotuzumab, when combined with chemotherapy, showed promising activity in treating recurrent/metastatic squamous cell cancer of the head and neck, with 67% of patients achieving objective responses, including complete and partial responses.

The combination therapy was associated with a higher frequency and severity of certain adverse events, such as neutropenia and anemia, compared to historical data, indicating that while effective, the treatment may increase the risk of chemotherapy-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of duligotuzumab (MEHD7945A) plus cisplatin/5-fluorouracil or carboplatin/paclitaxel for first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck. Jimeno, A., Machiels, JP., Wirth, L., et al.[2019]

In the phase II HAWK study involving 112 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) who had high PD-L1 expression, durvalumab showed an objective response rate of 16.2%, with a notably higher rate of 29.4% in HPV-positive patients.

Durvalumab was found to have an acceptable safety profile, with 57.1% of patients experiencing treatment-related adverse events, but none were fatal, indicating it could be a viable treatment option for this difficult-to-treat patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. Zandberg, DP., Algazi, AP., Jimeno, A., et al.[2020]

In a study of 14 heavily pretreated patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC), the combination of pembrolizumab and lenvatinib showed an objective response rate of 28.6%, indicating potential efficacy even in patients who had previously failed anti-PD-1 therapy.

The disease control rate was 42.9%, with an overall survival of 6.2 months and progression-free survival of 4.6 months, suggesting that this combination therapy may provide meaningful benefits for patients who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of pembrolizumab and lenvatinib is a potential treatment option for heavily pretreated recurrent and metastatic head and neck cancer. Chen, TH., Chang, PM., Yang, MH.[2021]

Chemotherapy remains the primary treatment for recurrent and metastatic head and neck squamous cell carcinoma, with the current standard being a combination of cisplatin, 5-fluorouracil, and cetuximab for fit patients.

Immunotherapy options like nivolumab and pembrolizumab have become new standards in second-line treatment, showing improved overall survival, but further research is needed to identify predictive markers for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. Karabajakian, A., Toussaint, P., Neidhardt, EM., et al.[2019]

Pembrolizumab has become the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), showing improved overall survival compared to traditional therapies like the EXTREME regimen.

The effectiveness of pembrolizumab is influenced by the PD-L1 expression level, with monotherapy recommended for patients with a PD-L1 combined positive score (CPS) ≥1, while those with lower CPS may benefit from the EXTREME regimen, highlighting the importance of personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the first-line treatment of advanced head and neck cancer. de Sousa, LG., Ferrarotto, R.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2599

A phase 1/2 study of retifanlimab (INCMGA00012, Anti–PD ... Here we report initial safety and efficacy results. Methods: Study consists of 4 parts in phase 1 and 2 expansion cohorts in phase 2. In phase 1 ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT402854

Phase 2 trial of retifanlimab (anti–PD-1) in combination ... This study aims to assess the efficacy and safety of the anti–PD-1 antibody, retifanlimab, in combination with INCAGN02385 (anti–LAG-3) and INCAGN02390 (anti– ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02680-1/fulltext

705TiP Phase II trial of retifanlimab (anti–PD-1) in ... This study aims to assess the efficacy and safety of the anti–PD-1 antibody retifanlimab in combination with INCAGN02385 (anti–LAG3) and INCAGN02390 (anti–TIM-3) ...

4. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05287113

UCSF Head and Neck Cancer Trial The purpose of this study is to evaluate the safety and efficacy of the combination of retifanlimab plus INCAGN02385 and retifanlimab plus INCAGN02385 and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12238943/

First-in-human phase I open-label study of the LAG-3 ... INCAGN02385 is a humanized monoclonal LAG-3-targeting antibody. This first-in-human phase I study evaluated INCAGN02385 for advanced/metastatic solid tumors.