Pembrolizumab for Adrenocortical Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, 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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy, pembrolizumab, to assess its effects on individuals with adrenocortical cancer (ACC) that cannot be surgically removed or has metastasized. Researchers aim to understand both the positive and negative effects of this treatment. Participants should have ACC that is not manageable with local treatments and must provide a tissue sample for biomarker analysis. The trial explores whether pembrolizumab can improve outcomes for those with challenging forms of ACC. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 immunosuppressive therapy within 7 days before starting the trial, unless it's for adrenal or pituitary insufficiency. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab is generally well-tolerated by people with advanced adrenocortical cancer. In one study, 17.9% of participants experienced serious side effects from the treatment. Some had to stop the treatment due to these side effects, yet still noticed some improvement in their condition.

Most participants managed the treatment without major problems. Pembrolizumab has demonstrated potential for long-term benefits and maintains a manageable safety profile. While some side effects can occur, many find them tolerable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it taps into the body's immune system to fight adrenocortical cancer. Unlike traditional chemotherapies that directly target and kill cancer cells, pembrolizumab is an immune checkpoint inhibitor. It blocks the PD-1 pathway, essentially taking the brakes off the immune system, allowing it to recognize and attack cancer cells more effectively. Researchers are excited about pembrolizumab because it offers a new way to treat this aggressive cancer, potentially leading to better outcomes for patients who may not respond well to conventional treatments.

What evidence suggests that pembrolizumab might be an effective treatment for adrenocortical cancer?

Research has shown that pembrolizumab, the treatment under study in this trial, can help treat advanced adrenocortical cancer. In some studies, patients experienced long-lasting positive effects, with a few seeing significant tumor shrinkage. Pembrolizumab boosts the immune system to better attack cancer cells. While results can vary, this treatment has shown promise for people with this type of cancer. ^{1 3 4 5 6}

Who Is on the Research Team?

Nitya Raj, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced adrenocortical carcinoma (ACC) that can't be removed or cured with surgery. Participants must have measurable disease, provide tissue for testing, and have good organ function. Women of childbearing age must test negative for pregnancy and agree to contraception; men also need to use birth control.

Inclusion Criteria

You have been diagnosed with advanced ACC that cannot be removed with surgery or treated effectively with local therapies.

You have a disease that can be measured using specific guidelines.

Be willing and able to provide written informed consent for the trial

Exclusion Criteria

Has received a live vaccine within 30 days prior to the first dose of trial treatment

If subject underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy

You have taken a specific type of medication in the last 4 weeks or have not fully recovered from side effects of a medication taken more than 4 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg as a 30-minute IV infusion every 3 weeks

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial is testing the effects of Pembrolizumab, an immunotherapy drug, on patients with ACC. The study aims to understand both the positive outcomes and any potential adverse effects this treatment may have on participants' cancer.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion Q3W.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Published Research Related to This Trial

A patient with advanced adrenocortical carcinoma, which typically has a poor prognosis, showed a positive radiographical response after being treated with pembrolizumab and mitotane for 15 months following first-line chemotherapy.

The treatment was well-tolerated, with no severe adverse events reported, suggesting that pembrolizumab may be a safe and effective second-line therapy for patients with microsatellite instability-high tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable response to pembrolizumab in microsatellite instability-high advanced adrenocortical carcinoma. Senda, M., Hashimoto, K., Shindo, T., et al.[2023]

In a retrospective review of six patients with metastatic adrenocortical carcinoma (ACC) who had previously failed mitotane and chemotherapy, the combination of pembrolizumab and mitotane showed promising results, with two patients achieving partial responses and four maintaining stable disease for 8 to 19 months.

All patients lived for at least 16 months after starting the combination therapy, indicating potential efficacy, and the treatment appeared effective in both microsatellite instability-high and stable tumors, suggesting a possible synergistic effect with mitotane.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer. Head, L., Kiseljak-Vassiliades, K., Clark, TJ., et al.[2020]

A 40-year-old woman with recurrent metastatic adrenocortical carcinoma (ACC) achieved a complete radiological response after 4 cycles of pembrolizumab combined with mitotane maintenance therapy, marking a significant treatment milestone.

This case suggests the potential efficacy of combining pembrolizumab, an immunotherapy, with mitotane in treating metastatic ACC, warranting further clinical trials to explore this combination's benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Radiological Response of Recurrent Metastatic Adrenocortical Carcinoma to Pembrolizumab and Mitotane. Alam, W., Bouferraa, Y., Haibe, Y., et al.[2021]

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 clinical trial involving 16 patients with metastatic adrenocortical carcinoma (ACC), pembrolizumab showed a modest non-progression rate of 36% at 27 weeks, indicating some effectiveness as a salvage therapy.

The treatment was generally well tolerated, with only 13% of patients experiencing severe adverse events, suggesting that pembrolizumab may be a safe option for patients with ACC despite limited overall efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma. Habra, MA., Stephen, B., Campbell, M., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31533818/

Phase II clinical trial of pembrolizumab efficacy and safety in ... Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma. J Immunother Cancer. 2019 Sep 18;7(1):253 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05563467

Pembrolizumab in the Treatment of Advanced, Progressive ... A Multicentre, Open-label Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab in the Treatment of Advanced, Progressive Adrenocortical Carcinoma.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.4112

Efficacy and safety of pembrolizumab in patients with ... Three pts achieving PR have completed 2 y of treatment with ongoing response noted. Tumor PD-L1 status is currently available in 6 pts with PR, ...

4. meridian.allenpress.com meridian.allenpress.com/innovationsjournals-JIPO/article/8/4/242/507946/Phase-2-Study-of-Monotherapy-with-Pembrolizumab

Phase 2 Study of Monotherapy with Pembrolizumab for ... Single-agent pembrolizumab in the treatment of advanced ACC has potential for durable responses and a manageable safety profile. More research ...

5. jitc.biomedcentral.com jitc.biomedcentral.com/articles/10.1186/s40425-019-0722-x

Phase II clinical trial of pembrolizumab efficacy and safety in ... Single-agent pembrolizumab has modest efficacy as a salvage therapy in ACC regardless of the tumor's hormonal function, microsatellite instability status, or ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05563467

Pembrolizumab in the Treatment of Advanced, Progressive ... Assessment of the safety of pembrolizumab (Keytruda) in the treatment of advanced, progressive adrenocortical carcinoma. Number of Adverse Events and Serious ...