Pembrolizumab for Solid Cancers

Not currently recruiting at 8 trial locations

Overseen By Yelena Janjigian, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

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

Disqualifiers: Metastatic disease, Active infection, Autoimmune disorders, 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

Duration: 12 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 or MK-3475) to determine if it can prevent cancer from returning in individuals who have had solid tumors removed. Participants will receive either pembrolizumab or a placebo for up to 12 months to assess its safety and effectiveness. The trial is open to those who have undergone surgery to remove a solid tumor but still have tumor cells detected in their blood. Individuals who recently completed standard cancer treatments and meet this profile may be suitable candidates for the trial. As an Early Phase 1 trial, this research aims to understand how pembrolizumab works in people, offering participants a chance to contribute to groundbreaking cancer treatment research.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment. It's best to discuss your specific medications with the trial team.

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

Research has shown that pembrolizumab is generally safe across different studies. A review of 31 trials found that many people with various solid cancers tolerate pembrolizumab well. Most side effects were mild to moderate, such as tiredness, itching, and rash, while serious side effects were less common.

As this trial is in its early stages, the main goal is to ensure the treatment's safety for participants. Although some evidence of safety exists, researchers continue to gather more information to fully understand it. Pembrolizumab is already used for other conditions, suggesting it is considered safe for those uses. However, safety in this specific trial remains under close observation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it harnesses the power of the immune system to fight solid cancers by blocking a specific protein called PD-1, which can help cancer cells hide from immune attack. Unlike traditional chemotherapy that directly kills fast-growing cells, pembrolizumab works by enabling the immune system to better recognize and destroy cancer cells. This targeted approach can potentially lead to fewer side effects and more personalized treatment options, making researchers excited about its potential to improve outcomes for patients with various types of solid tumors.

What evidence suggests that pembrolizumab might be an effective treatment for solid cancers?

Research has shown that pembrolizumab effectively treats certain cancers. For instance, in advanced melanoma, it reduced the risk of death by 29% over ten years. In patients with various solid tumors, some experienced significant benefits even after disease progression. Pembrolizumab also demonstrated effectiveness in patients with specific genetic markers, achieving a 39.1% response rate. These findings suggest that pembrolizumab might help prevent cancer recurrence in some patients after surgery. ^{6 7 8 9 10}

Who Is on the Research Team?

Yelena Janjigian, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults who've had surgery to remove a solid tumor with high microsatellite instability (MSI-H) and still have cancer cells in their blood. They must have completed standard cancer treatments, be generally healthy with good organ function, and not be on immunosuppressive drugs. People can't join if they're pregnant, breastfeeding, or have active infections like TB or hepatitis.

Inclusion Criteria

Albumin ≥3 mg/dL

Any solid tumor with MSI or MRD by IHC, PCR or NGS testing. MSKCC confirmation of MSI-H/MRD status is not mandatory prior to enrollment and treatment on the study. For patients with outside testing, if sufficient tissue is available NGS will be repeated at MSKCC and will not impact the patient's eligibility.

Must have genetic testing of DNA from primary tumor for somatic genomic alterations across a minimum of 50 genes.

Exclusion Criteria

Subjects with vitiligo or alopecia

Presence of metastatic or recurrent disease.

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.

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 IV every 3 weeks for up to 12 months

12 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for disease-free survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial is testing pembrolizumab's effectiveness at preventing cancer recurrence after surgery compared to a placebo. Participants will receive the drug or placebo for up to 12 months unless the cancer returns or side effects become too severe.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Pembrolizumab 200 mg IV every 3 weeks over 30 minutes.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Merck Sharp & Dohme LLC

Industry 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, 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]

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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

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, 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]

Citations

1. 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.

2. 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 ... KEYTRUDA demonstrated a sustained OS benefit, reducing the risk of death by 29% (HR=0.71 [95% CI, 0.60-0.85]). At 10 years, KEYTRUDA more than ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11229185/

Tumor dynamics in patients with solid tumors treated with ... Pembrolizumab generates meaningful efficacy in a subset of patients treated beyond disease progression per RECIST v1.1 guidelines.

4. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%). In KEYNOTE⁠-⁠671, adverse reactions ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38451314/

Clinical evidence for efficacy of pembrolizumab in MSI-H ... Of the 23 who received subsequent-line pembrolizumab, the ORR was 39.1%, disease control rate was 91.3%, and median PFS was 5.7 months (95% CI ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5628692/

Safety and efficacy profile of pembrolizumab in solid cancer The aim of the present review is to systematically evaluate the efficacy and safety of pembrolizumab by analyzing survival outcomes and at ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924000066

Safety profile of pembrolizumab monotherapy based on an ... This pooled analysis of 31 clinical trials showed that pembrolizumab has a consistent safety profile across indications.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02054806

NCT02054806 | Study of Pembrolizumab (MK-3475) in ... This study will assess the efficacy and safety of pembrolizumab (MK-3475) administered to participants with incurable advanced biomarker-positive solid tumors.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6527794/

Clinical utility of pembrolizumab in the management of ... Safety and efficacy profile of pembrolizumab in solid cancer: pooled reanalysis based on randomized controlled trials. Drug Des Devel Ther. 2017;11:2851 ...

10. merck.com merck.com/news/merck-announces-findings-from-phase-3-study-of-keytruda-pembrolizumab-compared-to-standard-of-care-in-patients-with-previously-treated-recurrent-or-metastatic-head-and-neck-squamous-cell-car/

Merck Announces Findings from Phase 3 Study of ... The findings include updated survival data showing a 19 percent reduction in the risk of death over standard treatment in the intent-to-treat population.