ADT + Pembrolizumab for Salivary Gland Cancer

Recruiting at 6 trial locations

Overseen By Amber Ryba

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Manish Patel

Must not be taking: Anti-PD-1, Anti-androgen

Disqualifiers: Pregnancy, Active infection, Autoimmune, 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: 15

Duration: 35 cycles (approximately 24 months)

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A Phase II, multi-center, single-arm, non-blinded study combining androgen deprivation therapy (ADT) and pembrolizumab for patients with metastatic or locally recurrent androgen receptor-positive salivary gland carcinoma, not amenable to surgery or radiation.

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, if you are on certain cancer treatments or immunosuppressive therapies, you may need to stop them before joining. It's best to discuss your specific medications with the trial team.

What safety information is available for the treatment with ADT and Pembrolizumab?

Pembrolizumab, also known as Keytruda, can cause immune-related side effects affecting various body systems, including skin, endocrine organs, and the mouth. Some rare side effects include glossitis (inflammation of the tongue) and type 1 diabetes, occurring in a small percentage of patients. ^{1 2 3 4 5}

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

This treatment combines pembrolizumab, an immune system-boosting drug that targets the PD-1 pathway, with goserelin acetate, a hormone therapy, offering a novel approach for salivary gland cancer, which has limited treatment options. ^{2 4 5 6 7}

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

Research shows that pembrolizumab has been effective in treating advanced salivary gland carcinoma, with some patients experiencing positive responses, including complete responses in certain cases. ^{1 4 6 8 9}

Who Is on the Research Team?

Manish Patel, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for adults with advanced salivary gland carcinoma that can't be removed by surgery or treated with radiation. Participants must have adequate organ function, no recent serious illnesses, and agree to use contraception. They should not have had certain prior treatments like anti-androgen therapy or immune checkpoint inhibitors.

Inclusion Criteria

Females of childbearing potential and males with partners of childbearing potential must be willing to abstain from heterosexual activity or to use a highly effect form of contraception from the time of informed consent until 8 months after treatment discontinuation.

My salivary gland cancer is confirmed to be androgen receptor-positive.

Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L

Exclusion Criteria

I am currently being treated for an infection.

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

I had palliative radiotherapy within the last week and have recovered from side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive androgen deprivation therapy (ADT) with goserelin acetate every 4 weeks and pembrolizumab every 3 weeks for up to 35 cycles

35 cycles (approximately 24 months)

Visits every 3 weeks for pembrolizumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

CT scans every 12 weeks

Optional Biopsy

An optional biopsy is performed after 4 doses of pembrolizumab to evaluate immune response

What Are the Treatments Tested in This Trial?

Interventions

• Goserelin Acetate
• Pembrolizumab

Trial Overview The study tests a combination of Androgen Deprivation Therapy (ADT) using Goserelin Acetate and Pembrolizumab in patients with androgen receptor-positive salivary gland cancer. It's a Phase II trial where all participants receive the same treatment without being compared to another group.

How Is the Trial Designed?

Group I: Goserelin Acetate + Pembrolizumab Experimental Treatment 2 Interventions

Goserelin Acetate, 3.6 mg, every four weeks, SQ Pembrolizumab, 200mg, every three weeks, IV

Goserelin Acetate is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Zoladex for:

• Breast cancer
• Prostate cancer
• Endometriosis
• Uterine fibroids

Approved in United States as Zoladex for:

• Advanced breast cancer
• Prostate cancer
• Endometriosis
• Uterine bleeding

Approved in Canada as Zoladex for:

• Breast cancer
• Prostate cancer
• Endometriosis

Who Is Running the Clinical Trial?

Manish Patel

Lead Sponsor

Trials

1

Recruited

20+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

TerSera Therapeutics LLC

Industry Sponsor

Trials

11

Recruited

1,300+

Published Research Related to This Trial

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]

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]

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]

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]

A patient with recurrent, platinum-refractory undifferentiated carcinoma of the parotid achieved a complete response after treatment with the checkpoint inhibitor Pembrolizumab.

This case highlights the potential efficacy of checkpoint inhibitors in treating challenging cases of undifferentiated carcinoma, suggesting a promising avenue for future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Three P's: Parotid, PD-L1, and Pembrolizumab. Wiggins, A., Arter, Z., Kerns, T.[2020]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

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]

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]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Citations

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

3. Greece pubmed.ncbi.nlm.nih.gov

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

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

Pembrolizumab-Induced Immune-Mediated Glossitis. [2022]

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

The Three P's: Parotid, PD-L1, and Pembrolizumab. [2020]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

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

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

New Approved Use for Keytruda. [2022]