Triple Drug Combo for Head and Neck Cancer

Recruiting at 102 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

176 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination for head and neck cancer?

Research shows that combining immunotherapy drugs like pembrolizumab with other treatments can improve outcomes for head and neck cancer patients. This suggests that using a combination of drugs, like in the trial, might enhance treatment effectiveness. ^{1 2 3 4 5}

How is the triple drug combo for head and neck cancer different from other treatments?

The triple drug combo for head and neck cancer, including INCAGN02385, INCAGN02390, and Retifanlimab, is unique because it combines multiple agents that may target different pathways in cancer cells, potentially offering a novel approach compared to existing treatments that often focus on single mechanisms like PD-1/PD-L1 blockade. ^{1 2 3 6 7}

Research Team

Matthias Bartenstein, MD

Principal Investigator

Incyte Corporation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England 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. [2020]

2. United States 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. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the first-line treatment of advanced head and neck cancer. [2022]

4. Netherlands 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. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Rational Combinations of Targeted Therapy and Immune Checkpoint Inhibitors in Head and Neck Cancers. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy of second-line chemotherapy or immune checkpoint inhibitors for patients with a prolonged objective response (≥ 6 months) after first-line therapy for recurrent or metastatic head and neck squamous cell carcinoma: a retrospective study. [2023]