Pembrolizumab + Cabozantinib for Head and Neck Cancer

Not currently recruiting at 1 trial location

Overseen By Nabil F. Saba, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Anticoagulants, Platelet inhibitors

Disqualifiers: HPV negative, Brain metastases, GI disorders, Cardiovascular disorders, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how pembrolizumab and cabozantinib can work together to help people with head and neck cancer that has recurred or metastasized and cannot be surgically removed. Pembrolizumab helps stop cancer cells from growing, while cabozantinib blocks certain pathways that cancer cells use to grow. The goal is to determine if these treatments together can improve outcomes for patients with this type of cancer. Suitable candidates for this trial have head and neck cancer that has returned or spread and have already tried other treatments without success. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like cytotoxic chemotherapy, biologic agents, and small molecule kinase inhibitors must not have been taken recently. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that pembrolizumab and cabozantinib are likely to be safe for humans?

Research shows that the combination of pembrolizumab and cabozantinib is generally well-tolerated by patients with head and neck cancer. Studies have found that this treatment can effectively manage the disease over an extended period and is considered safe. Some patients may experience side effects, but these are usually manageable. Previous patients demonstrated that this treatment is safe enough to warrant further research, indicating it is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab combined with cabozantinib for head and neck cancer because this treatment approach is quite different from standard options like chemotherapy, radiation, or surgery. Pembrolizumab is an immunotherapy that helps the body's immune system recognize and attack cancer cells, while cabozantinib is a targeted therapy that blocks specific pathways cancer cells use to grow. This combo could potentially tackle the cancer from two angles—boosting the immune response and directly inhibiting tumor growth. This dual action might provide a more effective treatment option with different side effects than traditional methods.

What evidence suggests that pembrolizumab and cabozantinib might be effective for head and neck cancer?

Research has shown that using pembrolizumab and cabozantinib together yields promising results for patients with head and neck squamous cell cancer. In this trial, participants will receive this combination treatment. Studies have found that this combination can help control the disease longer and improve survival rates. Early findings suggest these treatments work together to stop cancer cells from growing and spreading. Patients in previous studies experienced long-term benefits with a good safety record. Overall, evidence supports that this treatment combination may be effective for head and neck cancer that has returned or spread. ^{1 2 3 6}

Who Is on the Research Team?

Nabil F. Saba, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults with head and neck squamous cell cancer that's returned or spread and can't be surgically removed. They should have had some previous treatment, be in fairly good health (ECOG 0 or 1), not pregnant, willing to use contraception, and without certain medical conditions like major blood vessel invasion by the tumor or recent significant bleeding.

Inclusion Criteria

Serum phosphorus, calcium, magnesium and potassium ≥ LLN within 7 days before the first dose of cabozantinib

I understand the study requirements and have signed the consent form.

Disease progression must be documented following prior therapy

Exclusion Criteria

I haven't had radiation for bone metastasis in the last 2 weeks or any other radiation in the last 4 weeks.

I haven't had significant GI bleeding or coughed up blood recently.

I haven't had chemotherapy or biological treatment in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab IV on day 1 and cabozantinib PO daily for 21 days in 3-week cycles

Up to 2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib
• Pembrolizumab

Trial Overview The study tests pembrolizumab (a monoclonal antibody) combined with cabozantinib (which blocks pathways for cell growth) on patients with advanced head and neck cancer. The goal is to see if this combination improves tumor response compared to what's currently available.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab, cabozantinib) Experimental Treatment 2 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

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 phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

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]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

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]

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 phase 1b trial involving 60 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, pembrolizumab was found to be well tolerated, with only 17% experiencing severe drug-related adverse events and no drug-related deaths.

The treatment showed clinically meaningful antitumor activity, with an overall response rate of 18%, and particularly higher in HPV-positive patients at 25%, indicating its potential as a viable therapy for advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Seiwert, TY., Burtness, B., Mehra, R., et al.[2022]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03468218

NCT03468218 | Pembrolizumab & Cabozantinib in ... Giving pembrolizumab and cabozantinib may improve the chances of tumor response in patients with head and neck squamous cell cancer. Detailed Description.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39167623/

Long-term Survival Update with a Biomarker Analysis - PubMed Pembrolizumab and cabozantinib provided prolonged encouraging long-term disease control and survival with a maintained favorable safety profile.

3. onclive.com onclive.com/view/pembrolizumab-cabozantinib-combo-shows-promising-clinical-benefit-in-recurrent-metastatic-hnscc

Pembrolizumab/Cabozantinib Combo Shows Promising ... Data reported with pembrolizumab (Keytruda) plus cabozantinib (Cabometyx) demonstrated that the combination regimen is both highly active ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10205145/

Pembrolizumab and cabozantinib in recurrent metastatic head ... Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial

5. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35615

Promising long‐term disease control and survival with ... Promising long-term disease control and survival with pembrolizumab and cabozantinib for head and neck cancer. Mary Beth Nierengarten ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/30/20/4601/748808/Pembrolizumab-and-Cabozantinib-in-Recurrent-and-or

Pembrolizumab and Cabozantinib in Recurrent and/or ... Our findings confirm cabozantinib's robust clinical activity in head and neck squamous cell carcinoma (HNSCC) when combined with an anti-programmed cell death ...