Pembrolizumab Combinations for Cancer

Recruiting at 11 trial locations

Overseen By Toll Free Number

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Corticosteroids, Immunosuppressants, Anti-PD-1

Disqualifiers: Kaposi's sarcoma, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 3

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. ^{1 2 3 4 5}

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. ^{1 2 3 6 7}

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. ^{1 2 3 4 8}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Participants receive pembrolizumab in combination with investigational agents to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D)

Up to 21 days

Multiple visits for dose administration and monitoring

Efficacy Evaluation

Participants are evaluated for efficacy of the treatment using various response criteria

Up to 57 months

Regular visits every 3 weeks for up to 35 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 57 months

Treatment Details

Interventions

• Pembrolizumab

Trial Overview 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.

Participant Groups

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

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

Findings from Research

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 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 (MK-3475) is a monoclonal antibody that blocks PD-1, which helps the immune system fight cancer by preventing tumor cells from evading immune responses; it has shown high tumor response rates in advanced melanoma and non-small cell lung cancer.

The drug received accelerated FDA approval due to its effectiveness in early clinical trials, demonstrating long-lasting effects in patients who had previously been treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. McDermott, J., Jimeno, A.[2017]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., 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 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) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

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]

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

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

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

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

Pembrolizumab: PD-1 inhibition as a therapeutic strategy in cancer. [2017]

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]