Pembrolizumab + INCB081776 + Radiation for Head and Neck Cancer

Overseen By Cancer Connect

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Wisconsin, Madison

Must not be taking: Immunosuppressants

Disqualifiers: Auto-immune disease, Genetic conditions, Ophthalmologic disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: up to 12 months

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is evaluating INCB081776 when given in combination with the checkpoint inhibitor pembrolizumab and palliative radiation therapy in patients with metastatic or recurrent metastatic or recurrent head and neck squamous cell carcinoma (HNSCC). 12 participants will be enrolled and can expect to be on study for up to 12 months.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, prior cancer treatments must be completed at least 14 days before joining the trial, and you must have recovered from any side effects of those treatments.

What data supports the effectiveness of the drug pembrolizumab in treating head and neck cancer?

Pembrolizumab has shown antitumor activity in patients with recurrent or metastatic head and neck squamous cell carcinoma, with an objective response rate of 16% and some patients experiencing long-lasting responses. It is approved by the FDA for use in these patients after progression on platinum-containing chemotherapy. ^{1 2 3 4 5}

Is the combination of Pembrolizumab, INCB081776, and Radiation safe for humans?

Pembrolizumab has been studied for head and neck cancer and is generally considered to have manageable safety, with some serious side effects like pneumonia and thyroid disorders. It has been used safely in combination with radiation in clinical trials for head and neck cancer. ^{1 2 3 4 6}

What makes the drug combination of Pembrolizumab and INCB081776 with radiation unique for head and neck cancer?

This treatment is unique because it combines pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with INCB081776 and radiation, potentially enhancing the overall anti-cancer effect compared to standard treatments like cetuximab with radiation. ^{1 2 5 7 8}

Research Team

Justine Bruce, MD

Principal Investigator

University of Wisconsin, Madison

Deric Wheeler, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for people with metastatic or recurrent head and neck squamous cell carcinoma. Participants will be involved in the study for up to a year. Specific eligibility criteria are not provided, but typically include factors like age, health status, and cancer stage.

Inclusion Criteria

My disease cannot be removed by surgery and has at least one area that can be measured for treatment progress.

I am willing to provide at least 2 research biopsies during the study.

I have two tumors that need radiation and can be biopsied.

Exclusion Criteria

Subjects with significant intercurrent illnesses per physician discretion

I am being treated with immunosuppressants for an autoimmune disease.

I have a known eye or vision condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INCB081776 in combination with pembrolizumab and palliative radiation therapy. Cycle 1 is 56 days, and subsequent cycles are 21 days each.

up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including the evaluation of adverse events.

4-5 weeks

Treatment Details

Interventions

• INCB081776
• Palliative RT
• Pembrolizumab

Trial Overview The study tests INCB081776 combined with pembrolizumab (a checkpoint inhibitor) and palliative radiation therapy. The goal is to see how well these treatments work together in patients with advanced head and neck cancer.

Participant Groups

Group I: INCB081776/Pembrolizumab and RT for HNSCC Experimental Treatment 3 Interventions

Cycle 1 of this clinical trial is 56 days in duration to allow for the systematic addition of each agent to the combination regimen. For cycle 2 and all subsequent cycles, the treatment cycle will be 21 days in length.

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials

312

Recruited

853,000+

Findings from Research

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a phase 3 study involving 495 patients with recurrent or metastatic head-and-neck squamous cell carcinoma, pembrolizumab demonstrated a median overall survival of 8.4 months, compared to 6.9 months for standard-of-care treatments, indicating a significant improvement in survival rates.

Pembrolizumab was associated with fewer severe treatment-related adverse events (13%) compared to standard-of-care therapies (36%), suggesting a better safety profile for patients receiving pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Cohen, EEW., Soulières, D., Le Tourneau, C., et al.[2019]

A 69-year-old patient with relapsed squamous cell carcinoma showed significant improvement after 14 cycles of pembrolizumab, indicating its efficacy as a second-line treatment for metastatic head and neck cancer.

The patient developed severe immune-related adverse effects, specifically grade 4 mucositis and esophagitis, highlighting the importance of monitoring for such complications in patients receiving PD-1 inhibitors like pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab. Acero Brand, FZ., Suter, N., Adam, JP., et al.[2019]

In a phase III trial, pembrolizumab, a single-agent treatment, showed significant effectiveness in patients with head and neck tumors that had high PD-L1 expression, leading to deep and lasting responses.

This study highlights the potential of pembrolizumab as a first-line therapy for this specific group of cancer patients, suggesting a targeted approach based on PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembro Ups Survival in PD-L1-positive HNSCC. [2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. [2023]

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

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. [2019]

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

Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Pembro Ups Survival in PD-L1-positive HNSCC. [2019]