Pembrolizumab for Cancer of Unknown Primary

(CUP Trial)

Not currently recruiting at 2 trial locations

Overseen By Kelsey Meyer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AHS Cancer Control Alberta

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Active infection, 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

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

Compensation: Varies

Number of Visits: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called pembrolizumab (also known as KEYTRUDA) for individuals with metastatic cancer where the primary cancer site remains unidentified. The goal is to determine if pembrolizumab, administered through an IV every three weeks, can manage this challenging condition. It targets those who haven't received cancer treatment yet and have adenocarcinoma, poorly differentiated carcinoma, or certain squamous cell carcinomas. Individuals diagnosed with one of these and have measurable disease on a scan might find this trial suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of Pembrolizumab.

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

Research shows that pembrolizumab is generally safe for people with cancer. Studies have found that patients with cancer of unknown primary (CUP) experienced few serious side effects when using pembrolizumab. In previous research, pembrolizumab was tested in patients with advanced cancer, and most tolerated the treatment well.

Common side effects of pembrolizumab include tiredness, itching, and diarrhea, which are usually mild and manageable. Serious side effects are less common but can occur. Monitoring health and reporting any unusual symptoms to a doctor is important.

Since pembrolizumab is already approved for other cancers, extensive safety information is available. This trial aims to further study its safety in patients with CUP. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it targets the PD-1 pathway, a mechanism that helps the immune system recognize and fight cancer cells. Unlike traditional chemotherapy, which attacks rapidly dividing cells in general, pembrolizumab specifically enhances the body's immune response against cancer. This precision reduces damage to healthy cells and potentially leads to fewer side effects. Researchers are excited about pembrolizumab for cancer of unknown primary because it offers a new way to treat these elusive cancers, potentially leading to better outcomes for patients who previously had limited treatment options.

What evidence suggests that pembrolizumab might be an effective treatment for carcinoma of unknown primary?

Research has shown that pembrolizumab, which participants in this trial will receive, holds promise for patients with cancer of unknown primary (CUP). Studies have found it effective for many with this condition. Pembrolizumab is generally safe and enhances the body's immune system to fight cancer more effectively. Although further research is ongoing, initial findings offer hope for those with CUP. ^{3 5 6 7 8}

Who Is on the Research Team?

Jose Monzon, MD

Principal Investigator

Arthur J.E. Child Comprehensive Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults with metastatic carcinoma of unknown primary site (CUP) who haven't had prior cancer treatments. Participants need to have a specific performance status, provide tissue samples, and use contraception if applicable. Excluded are those with certain other cancers or conditions, recent immunosuppressive therapy, active infections, known allergies to Pembrolizumab components, or CNS metastases.

Inclusion Criteria

I agree to use two forms of birth control during and for 120 days after the study.

My cancer's origin is unknown, but I've undergone tests to try to find its source.

My cancer can be measured by scans.

Exclusion Criteria

My cancer is suspected to be a specific type based on certain tests.

I am currently being treated for an infection.

I have been treated with drugs targeting PD-1, PD-L1, or PD-L2.

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 intravenously every 3 weeks for up to 24 months

24 months

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests Pembrolizumab injections given intravenously every three weeks for up to two years in patients with poor-prognosis CUP. It's a phase 2 trial without a control group where all 25 participants receive the same treatment to evaluate its effectiveness and safety.

How Is the Trial Designed?

Group I: Arm 1 - Pembrolizumab Experimental Treatment 1 Intervention

Arm 1 - Pembrolizumab injection dosed at 200 mg given Q3 weeks by IV infusion on Day 1 of each 3 week cycle.

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?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Tom Baker Cancer Centre

Collaborator

Trials

30

Recruited

8,900+

Published Research Related to This Trial

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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., 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]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

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 is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35618285/

Efficacy of pembrolizumab in patients with advanced cancer of ... Conclusion: Pembrolizumab showed encouraging efficacy in patients with CUP with acceptable safety profile. Trial registration number: NCT02721732.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.TPS3103

Phase II study for the evaluation of efficacy ... Phase II study for the evaluation of efficacy of pembrolizumab (MK-3475) in patients with cancer of unknown primary. Authors: Gauri R. Varadhachary, Kanwal ...

3. jitc.bmj.com jitc.bmj.com/content/10/5/e004822

a phase 2 non-randomized clinical trial Pembrolizumab has encouraging clinical activity with an acceptable safety profile in patients with previously treated CUP. Introduction. Cancer ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12357449/

Clinical efficacy of immune checkpoint inhibitors for cancer ... Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): a phase 2 non-randomized clinical trial. J Immunother ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9125753/

Efficacy of pembrolizumab in patients with advanced cancer of ... Tumor response and survival outcomes on pembrolizumab in patients with cancer of unknown primary. (A) (Spider plot) shows the change in sum ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

8. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...