Bavituximab + Pembrolizumab for Head and Neck Cancer

Overseen By Ranee Mehra, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

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: 21

Duration: 100 weeks

7 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II single arm study is being done to determine if bavituximab could potentially synergize with PD-1 inhibitor therapy to generate an effective anti-tumor immune response in patients with recurrent/metastatic squamous cell head and neck cancer (HNSCC) who progressed on a PD-1 inhibitor.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Bavituximab + Pembrolizumab for head and neck cancer?

Research shows that Pembrolizumab, one of the drugs in the treatment, is effective for head and neck cancer, especially in patients whose tumors have high levels of a protein called PD-L1, which is linked to better responses. ^{1 2 3 4 5}

Is the combination of Bavituximab and Pembrolizumab safe for treating head and neck cancer?

Pembrolizumab, also known as KEYTRUDA, has been studied for safety in patients with head and neck cancer. Common serious side effects include pneumonia (lung infection), breathing difficulties, confusion, vomiting, fluid around the lungs, and respiratory failure. Other significant side effects can involve the immune system, affecting the lungs, colon, liver, adrenal glands, blood sugar levels, skin, muscles, and thyroid. ^{2 3 6 7 8}

What makes the drug combination of Bavituximab and Pembrolizumab unique for head and neck cancer?

The combination of Bavituximab and Pembrolizumab is unique because it pairs an anti-PD-1 agent (Pembrolizumab) with Bavituximab, which may offer a novel approach to enhance the immune system's ability to fight head and neck cancer, unlike other treatments that typically combine Pembrolizumab with different types of drugs like chemotherapeutics or other antibodies. ^{4 9 10 11 12}

Eligibility Criteria

This trial is for adults over 18 with recurrent/metastatic squamous cell head and neck cancer who've seen their cancer progress after platinum therapy and PD-1 inhibitor treatment. They must have measurable disease, provide a recent tumor tissue sample, have good performance status (0 or 1), adequate organ function, agree to use contraception, and not be pregnant.

Inclusion Criteria

Have measurable disease based on RECIST 1.1

My head and neck cancer has worsened after treatment with drugs like nivolumab or pembrolizumab.

My cancer got worse after platinum therapy or within 6 months of cisplatin and radiation treatment.

Exclusion Criteria

I have a history of active tuberculosis.

I am currently being treated for an infection.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and bavituximab for progressive recurrent/metastatic squamous cell carcinoma of the head and neck

100 weeks

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

55 months

Treatment Details

Interventions

• Bavituximab
• Pembrolizumab

Trial Overview The study tests if bavituximab can enhance the immune response when combined with pembrolizumab in patients whose cancers progressed on prior PD-1 inhibitors. It's a phase II single-arm trial where all participants receive both drugs.

Participant Groups

Group I: Pembrolizumab + Bavituximab Experimental Treatment 2 Interventions

Pembro and Bavituximab for progressive recurrent/metastatic squamous cell carcinoma of head and neck

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

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 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]

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 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]

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]

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]

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 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]

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]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

A cost-effectiveness analysis of nivolumab versus pembrolizumab in treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) found that nivolumab has a 56% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted life-year (QALY) when dosed at 3 mg/kg biweekly for patients under 72 kg.

For patients over this weight, pembrolizumab is generally the more cost-effective option, especially at higher WTP thresholds, indicating that patient body weight and dosing strategy are crucial factors in treatment decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis. Pei, R., Shi, Y., Lv, S., et al.[2021]

References

1. England 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. [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

Pembrolizumab alone or with chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: Health-related quality-of-life results from KEYNOTE-048. [2022]

4. 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]

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

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

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

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]

8. England 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. [2022]

9. 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]

10. United States 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. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. [2022]

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

Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis. [2021]