Subcutaneous vs Intravenous Pembrolizumab for Cancer

Not currently recruiting at 50 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretrovirals, Hepatitis B antivirals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Small cell lung cancer, Active CNS metastases, Active autoimmune disease, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether patients prefer receiving cancer treatment with pembrolizumab (also known as KEYTRUDA, an immunotherapy drug) as a subcutaneous injection or through an IV drip. It targets patients with specific cancers, including resected melanoma, resected renal cell carcinoma, and advanced non-small cell lung cancer. Participants will experience both methods and then select their preferred one for continued treatment. This trial may suit individuals with a confirmed solid tumor who have not recently undergone certain cancer treatments or major surgeries. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pembrolizumab, administered either intravenously (IV) or subcutaneously (SC), is generally well-tolerated. The IV form of pembrolizumab is already approved for treating several cancers, such as non-small cell lung cancer (NSCLC) and melanoma, proving its safety for many patients. Studies have found that the SC version, which uses an enzyme called berahyaluronidase alfa to aid absorption, is also safe.

Research on SC pembrolizumab combined with chemotherapy found safety results similar to the IV form. While side effects can occur, such as injection site reactions or flu-like symptoms, they are usually manageable. Over 4,000 patients have been studied with IV pembrolizumab, demonstrating its reliable safety record for various conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the new approach to delivering pembrolizumab for conditions like renal cell carcinoma, melanoma, and non-small cell lung cancer because it introduces a subcutaneous (SC) delivery method. Unlike traditional intravenous (IV) infusions, the SC method, combined with berahyaluronidase alfa, could offer a more convenient and potentially quicker administration for patients. This new delivery method might not only improve the patient experience by reducing time spent in clinics but also make pembrolizumab more accessible, especially in settings where IV administration is challenging.

What evidence suggests that subcutaneous pembrolizumab could be effective for cancer?

Research has shown that pembrolizumab effectively treats various cancers, such as non-small cell lung cancer (NSCLC) and melanoma, whether administered subcutaneously or intravenously. This trial will compare these two methods. Participants in Arm A will receive pembrolizumab combined with berahyaluronidase alfa subcutaneously, followed by pembrolizumab intravenously. Participants in Arm B will receive pembrolizumab intravenously, followed by the subcutaneous combination. Studies have found that both methods are similarly effective and safe. For instance, one study found that subcutaneous pembrolizumab combined with chemotherapy works as well as the intravenous form. Additionally, intravenous pembrolizumab has helped some lung cancer patients live longer. Both forms are trusted options for treating these cancers and have a proven record of improving patient outcomes. ^{2 5 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for people with certain types of cancer (like lung, melanoma, or kidney) who have a life expectancy of at least 3 months and are in good physical condition. They must not have had severe reactions to pembrolizumab before, no active infections or autoimmune diseases needing recent treatment, and should not be on immunosuppressants.

Inclusion Criteria

You have hepatitis B, but you may still be able to participate if you meet certain requirements.

My HIV is well controlled with medication.

My cancer type and stage match the trial's specific requirements.

Exclusion Criteria

I have or had lung inflammation that needed steroids.

I am still recovering from major surgery or have complications.

My lung cancer is non-small cell, but it also has small cell elements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Crossover

Participants receive both subcutaneous and intravenous formulations of pembrolizumab in a crossover design

Up to ~106 days

Treatment Continuation

Participants receive their preferred intervention for up to 1 year for RCC and melanoma, and up to 2 years for NSCLC

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 27 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview

The study compares participant preference between two ways of getting Pembrolizumab: a new method mixed with hyaluronidase given under the skin versus the usual way through an IV. The goal is to see which method patients like more without testing effectiveness.

How Is the Trial Designed?

Group I: Arm A: Pembrolizumab (+) Berahyaluronidase alfa SC →Pembrolizumab IV Experimental Treatment 2 Interventions

In the treatment crossover period, participants will receive pembrolizumab (+) berahyaluronidase alfa SC followed by pembrolizumab IV. After completion of the treatment crossover period, participants will enter the treatment continuation period, where they will receive their preferred intervention for up to \~1 year for renal cell carcinoma (RCC) and melanoma and for up to \~2 years for non-small cell lung cancer (NSCLC).

Group II: Arm B: Pembrolizumab IV→pembrolizumab (+) berahyaluronidase alfa SC Active Control 2 Interventions

In the treatment crossover period, participants will receive pembrolizumab IV followed by pembrolizumab (+) berahyaluronidase alfa SC. After completion of the treatment crossover period, participants will enter the treatment continuation period, where they will receive their preferred intervention for up to \~1 year for RCC and melanoma and for up to \~2 years for NSCLC.

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?

Merck Sharp & Dohme LLC

Lead 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

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]

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, 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 (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 (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., 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, 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]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

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]

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Pembrolizumab (intravenous route) - Side effects & uses

It is given through an IV catheter placed into one of your veins. It must be given slowly, so the IV will have to remain in place for at least 30 minutes.

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