Pembrolizumab Combinations for Cancer

Recruiting in Palo Alto (17 mi)

+11 other locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Merck Sharp & Dohme LLC

No Placebo Group

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study is a rolling arm study of pembrolizumab in combination with investigational agents in pediatric participants with relapsed or refractory classical Hodgkin lymphoma (cHL) solid tumors with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) or tumor mutational burden-high (TMB-H). This study will have 2 parts: a safety lead-in to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D) (Part 1) followed by an efficacy evaluation (Part 2). Participants will be assigned to a treatment arm (either Part 1 or Part 2) that is open for enrollment. There will be no hypothesis testing in this study.

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 have received prior systemic anticancer therapy within 4 weeks before the first dose, or radiotherapy within 2 weeks. Also, you cannot be on chronic systemic steroid therapy exceeding 10 mg daily of prednisone equivalent within 7 days prior to the first dose.

What data supports the idea that Pembrolizumab Combinations for Cancer is an effective drug?

The available research shows that Pembrolizumab, when used in combination with other treatments, has shown effectiveness in treating certain types of cancer. For example, in a study involving patients with melanoma, Pembrolizumab demonstrated high response rates with minimal side effects. Additionally, it has been approved for use in non-small cell lung cancer and melanoma due to its ability to help the immune system fight cancer cells. In comparison to other treatments, Pembrolizumab has shown promising results in terms of tumor response and duration of effect, making it a valuable option for patients with these cancers.

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What safety data is available for Pembrolizumab (Keytruda)?

Pembrolizumab, also known as Keytruda, has been evaluated in various clinical trials for its safety profile. In a phase II trial for non-small cell lung cancer, an interim safety analysis was conducted. Pembrolizumab has shown clinical activity in multiple solid tumors, including thoracic malignancies, with ongoing studies to confirm its benefits. However, it can cause immune-mediated adverse reactions such as pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. In a phase 1 trial for metastatic melanoma, common adverse reactions included fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Despite these risks, the benefits of pembrolizumab, such as prolonged response durations, have been considered to outweigh the risks in life-threatening conditions.

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Is the drug Pembrolizumab a promising treatment for cancer?

Yes, Pembrolizumab is a promising drug for cancer treatment. It has shown positive results in treating various cancers, including lung cancer, melanoma, and esophageal cancer. It works by helping the immune system fight cancer cells more effectively. Pembrolizumab has been approved for use in several types of cancer and is being tested in many others, showing high response rates and long-lasting effects.

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Eligibility Criteria

This trial is for young people with certain blood cancers or solid tumors that haven't responded to other treatments. Participants must have recovered from side effects of previous cancer therapies and have specific diagnoses like relapsed Hodgkin lymphoma, advanced melanoma, or tumors with high mutational burden.

Inclusion Criteria

My cancer is one of: relapsed Hodgkin lymphoma, advanced melanoma, MSI-H/dMMR, or TMB-H solid tumors.

I have recovered from side effects of previous cancer treatments.

I have HIV and it is well-controlled with medication.

Exclusion Criteria

I have another cancer that has not needed treatment in the last year.

I have active brain metastases or carcinomatous meningitis.

I am currently being treated for an infection.

Participant Groups

The study tests Pembrolizumab in combination with new drugs (Vibostolimab, Favezelimab) on pediatric patients. It has two parts: first ensuring the treatment is safe and finding the right dose, then checking how well it works. Patients are placed into either part based on what's currently available.

Group I: Pembrolizumab/Vibostolimab Experimental Treatment 1 Intervention

Participants will receive coformulated pembrolizumab/vibostolimab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.

Group II: Pembrolizumab + Vibostolimab Experimental Treatment 2 Interventions

Participants will receive pembrolizumab and vibostolimab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.

Group III: Favezelimab/Pembrolizumab Experimental Treatment 1 Intervention

Participants will receive coformulated favezelimab/pembrolizumab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.

Group IV: Favezelimab + Pembrolizumab Experimental Treatment 2 Interventions

Participants will receive pembrolizumab and favezelimab via an intravenous (IV) infusion every 3 weeks (Q3W) for up to 35 cycles. Each cycle is 21 days.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Intermountain - Primary Children's Hospital ( Site 2014) Salt Lake City, UT

Children's Mercy Hospital ( Site 2024) Kansas City, MO

Children's Hospital of Philadelphia (CHOP) ( Site 2021) Philadelphia, PA

Yale-New Haven Hospital ( Site 2012) New Haven, CT

More Trial Locations

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC Lead Sponsor

References

1. 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] A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017] New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017] Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.

4. Spain pubmed.ncbi.nlm.nih.gov

Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. [2017] Programmed cell death protein 1 (PD-1) and its ligands, programmed cell death 1 ligand 1 (PD-L1) and 2 (PD-L2) play an important role in regulating immune response through various mechanisms. This inhibitory action is thought to assist in immune evasion by cancer cells as PD-1, PD-L1 and PD-L2 have been found to be abnormally expressed by tumor cells and lymphocytes in the tumor microenvironment. Preclinical studies described PD-1 blockade resulting in tumor growth suppression and even decreased metastasis. This has led to the development of pembrolizumab (MK-3475), a highly selective, humanized monoclonal IgG4-kappa isotype antibody against PD-1. Early clinical trials have shown high tumor response rates and long duration of effect in previously treated advanced melanoma resulting in accelerated FDA approval for the drug in this situation. Pembrolizumab has also had success in non-small cell lung cancer and is being tested in multiple other tumor types. This review will discuss the development, preclinical data, pharmacokinetics and clinical efficacy to date of pembrolizumab.

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022] To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer.

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023] Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021] On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp &amp; Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (&#8805;20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. &#169;2017 AACR.

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023] Pembrolizumab (Keytruda) has been approved to treat metastatic or locally advanced esophageal or gastroesophageal junction cancer. It is used in combination with platinum- and fluoropyrimidine-based chemotherapy.