Pembrolizumab Combinations for Cancer

No longer recruiting at 13 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of pembrolizumab (also known as KEYTRUDA, an immunotherapy drug) combined with other investigational treatments for children and teens with certain difficult-to-treat cancers. The focus is on relapsed or hard-to-treat classical Hodgkin lymphoma and other solid tumors with specific genetic markers that make them more challenging. Participants will receive different treatment combinations to determine which works best. This trial suits those with these cancer types who have not succeeded with other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

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.

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

Research has shown that using pembrolizumab with vibostolimab has a safety profile similar to each drug used alone. In studies, patients with advanced cancers found the side effects of this combination manageable. Most side effects were mild, such as fatigue and nausea.

For the combination of favezelimab with pembrolizumab, studies have also shown a consistent safety profile. The side effects were similar to those expected from each drug alone, with common side effects including fatigue and mild skin rash.

Both combinations remain under study, but current data suggest they are generally well-tolerated by patients. This information is important for anyone considering joining a clinical trial for these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine pembrolizumab, a well-known immune checkpoint inhibitor, with new agents like vibostolimab and favezelimab. Unlike standard cancer treatments that typically focus on chemotherapy or radiation, these combinations aim to enhance the immune system's ability to fight cancer. Vibostolimab and favezelimab target different immune pathways, potentially providing a more robust and sustained immune response. Additionally, the coformulated versions offer a streamlined administration process, making it potentially more convenient for patients. This innovative approach could lead to improved outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for relapsed or refractory classical Hodgkin lymphoma?

This trial will evaluate different combinations of pembrolizumab with other agents. Research has shown that using pembrolizumab with vibostolimab, one of the combinations in this trial, has promising effects against tumors, especially in non-small-cell lung cancer. Patients with advanced cancers that have a specific genetic feature (called dMMR) experienced long-lasting positive responses to this treatment. However, in some cancers like cervical cancer, this combination did not outperform pembrolizumab alone.

Another combination in this trial is favezelimab and pembrolizumab. Studies have found a higher response rate and more tumor shrinkage with this combination compared to pembrolizumab alone. This suggests that favezelimab might enhance pembrolizumab's effectiveness in certain cancers. Still, in some cases, this combination did not extend patient survival compared to other treatments. ^{1 2 3 4 6}

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 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 experiencing or being treated for GVHD.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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]

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 (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]

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) 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 (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]

Citations

1. merck.com merck.com/news/merck-provides-update-on-phase-3-keyform-007-trial-evaluating-investigational-fixed-dose-combination-of-favezelimab-and-pembrolizumab-for-patients-with-previously-treated-pd-l1-positive-microsatellite/

Merck Provides Update on Phase 3 KEYFORM-007 Trial ... The Phase 3 KEYFORM-007 trial evaluating the investigational fixed-dose combination of favezelimab, Merck's anti-LAG-3 antibody, and pembrolizumab (KEYTRUDA)

2. ashpublications.org ashpublications.org/bloodadvances/article/9/19/4987/546200/Estimating-efficacy-of-favezelimab-plus

Estimating efficacy of favezelimab plus pembrolizumab ... Favezelimab plus pembrolizumab had a higher response rate and greater reduction in tumor burden vs pembrolizumab alone. Results suggest ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12514497/

Estimating efficacy of favezelimab plus pembrolizumab ... Favezelimab plus pembrolizumab had a higher response rate and greater reduction in tumor burden vs pembrolizumab alone. Results suggest favezelimab ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05064059

NCT05064059 | A Study of Coformulated Favezelimab/ ... The primary study hypothesis is that coformulated favezelimab/pembrolizumab (MK-4280A) is superior to standard of care with respect to overall survival.

5. onclive.com onclive.com/view/fixed-dose-favezelimab-combo-fails-to-improve-os-in-pretreated-pd-l1-mss-mcrc

Fixed-Dose Favezelimab Combo Fails to Improve OS in ... The combination of favezelimab and pembrolizumab failed to improve OS vs regorafenib or TAS-102 in pretreated patients with PD-L1–positive, MSS mCRC.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9832734/

A first-in-human study of the anti-LAG-3 antibody ... Here, we evaluate the antitumor activity of the LAG-3 antibody favezelimab alone or in combination with pembrolizumab in participants with MSS mCRC.