Pemetrexed + Pembrolizumab for Salivary Gland Cancer

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active infection, Autoimmune disease, 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

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

Compensation: Varies

Number of Visits: 24

Duration: 2 years

45 Participants Needed

Trial Summary

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have used immunosuppressive medication within 14 days before joining, and certain conditions like active infections or autoimmune diseases requiring treatment might affect eligibility. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug pembrolizumab for salivary gland cancer?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, has been studied for advanced salivary gland cancer and other types of cancer. It has shown promise in treating salivary gland cancer, especially when the cancer cells have certain markers (PD-L1) that pembrolizumab targets. ^{1 2 3 4 5}

Is the combination of Pemetrexed and Pembrolizumab generally safe for humans?

Pembrolizumab (also known as Keytruda) has been used in various cancer treatments and can cause side effects affecting different body systems, such as skin issues and immune-related reactions. In some cases, it has led to conditions like glossitis (inflammation of the tongue), which improved with treatment. Safety data from studies on other cancers suggest it is generally safe, but side effects can occur. ^{1 2 3 4 5}

How is the drug Pemetrexed + Pembrolizumab unique for treating salivary gland cancer?

This drug combination is unique because there are no proven systemic therapies for salivary gland cancer, and Pemetrexed has not been previously used for this condition, while Pembrolizumab has shown promise in treating similar cancers. ^{1 3 5 6 7}

What is the purpose of this trial?

This phase II trial studies the effect of pemetrexed and pembrolizumab in treating patients with salivary gland cancer that has come back (recurrent) and/or has spread to other places in the body (metastatic). Chemotherapy drugs, such as pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to evaluate whether pembrolizumab, an immunotherapy drug, in combination with the chemotherapy drug, pemetrexed, has an effect on advanced salivary gland cancer.

Research Team

Katherine A. Price, MD

Principal Investigator

Mayo Clinic in Rochester

Ashish Chintakuntlawar, MBBS, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults with advanced salivary gland cancer that has returned or spread and can't be cured by surgery. They should have a life expectancy of at least 12 weeks, good organ function, no severe illnesses that could interfere with the study, and must agree to use contraception. Prior treatments are allowed but there are restrictions on recent surgeries, therapies, and certain medications.

Inclusion Criteria

Willingness to provide mandatory blood specimens for correlative research

Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement) (obtained =< 8 days prior to registration)

Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 8 days prior to registration)

Exclusion Criteria

I have had pneumonitis treated with steroids or currently have it.

I have not received any live vaccines or been part of a drug study in the last 4 weeks.

I have received an organ or tissue transplant from another person.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and pemetrexed intravenously every 21 days for up to 35 cycles (2 years) in the absence of disease progression or unacceptable toxicity

2 years

Every 21 days

Extension

Participants with stable disease, partial response, or complete response may continue pembrolizumab for an additional 17 cycles (1 year) in the absence of disease progression or unacceptable toxicity

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 years

Every 3 months

Treatment Details

Interventions

• Pembrolizumab
• Pemetrexed Disodium

Trial Overview The trial is testing the combination of pemetrexed (a chemotherapy drug) and pembrolizumab (an immunotherapy antibody) in patients with recurrent or metastatic salivary gland cancer. The goal is to see if this combo can stop cancer cells from growing by killing them directly or boosting the immune system's response.

Participant Groups

Group I: Treatment (pembrolizumab, pemetrexed) Experimental Treatment 7 Interventions

Patients receive pembrolizumab IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Cycles of pemetrexed disodium repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who had stable disease, partial response, or complete response after completion of 35 cycles of pembrolizumab, may continue pembrolizumab for an additional 17 cycles (1 year) in the absence of disease progression or unacceptable toxicity. Patients additionally undergo blood sample collection, CT, PET/CT or MRI and may also undergo PSMA PET on study.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase 2 study of 109 patients with advanced salivary gland carcinoma, pembrolizumab showed a modest objective response rate of 4.6%, with a higher response of 10.7% in patients with PD-L1-positive tumors, indicating some efficacy in this specific subgroup.

The treatment was generally well-tolerated, with 75.2% of patients experiencing treatment-related adverse events, mostly manageable, and no grade 5 events reported, suggesting a favorable safety profile for pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab monotherapy in patients with previously treated advanced salivary gland carcinoma in the phase 2 KEYNOTE-158 study. Even, C., Delord, JP., Price, KA., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody used for treating various cancers, can cause immune-related adverse events (IRAEs) affecting multiple body systems, including rare oral mucosal issues like glossitis.

In a case study of a 71-year-old male with lung cancer, treatment with oral prednisone effectively improved tongue ulcerations caused by pembrolizumab, highlighting the need for awareness of such rare side effects and their management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-Induced Immune-Mediated Glossitis. Alias, A., Hall, JA., Kulkarni, P., et al.[2022]

In a phase Ib trial involving 26 patients with advanced, PD-L1-positive salivary gland carcinoma, pembrolizumab showed a confirmed objective response rate of 12%, indicating some antitumor activity after a median follow-up of 20 months.

The treatment was generally manageable in terms of safety, with 85% of patients experiencing treatment-related adverse events, though serious complications occurred, including one death due to interstitial lung disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of the Phase 1b KEYNOTE-028 Study. Cohen, RB., Delord, JP., Doi, T., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

This study presents the first evidence of pemetrexed being effective as a treatment for metastatic adenocarcinoma of the salivary glands, based on case reports of two patients.

Both patients showed significant and sustained clinical responses, with one experiencing an 8-month response after multiple previous treatments, suggesting that pemetrexed could be a promising option for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marked responses to pemetrexed chemotherapy for metastatic adenocarcinoma of the parotid gland: Case series. Viscuse, PV., Price, K.[2020]

A 73-year-old woman with recurrent parotid cancer showed a significant partial response to 14 cycles of pembrolizumab, indicating its potential efficacy in treating this rare cancer type.

The treatment was generally well-tolerated, with only a mild immune-related adverse event (grade 1 pneumonia), suggesting a favorable safety profile for pembrolizumab in this patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Recurrent Metastatic Parotid Acinic Cell Carcinoma Responsive to Pembrolizumab. Yamashita, G., Okamoto, I., Shimizu, A., et al.[2022]

References

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

Evaluation of pembrolizumab monotherapy in patients with previously treated advanced salivary gland carcinoma in the phase 2 KEYNOTE-158 study. [2022]

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

Pembrolizumab-Induced Immune-Mediated Glossitis. [2022]

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

Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of the Phase 1b KEYNOTE-028 Study. [2021]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

5. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Marked responses to pemetrexed chemotherapy for metastatic adenocarcinoma of the parotid gland: Case series. [2020]

7. Greece pubmed.ncbi.nlm.nih.gov

A Case of Recurrent Metastatic Parotid Acinic Cell Carcinoma Responsive to Pembrolizumab. [2022]