Pembrolizumab for Advanced Cancers

Recruiting at 880 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Pembrolizumab, Lenvatinib

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

3500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, an immunotherapy drug, for people with advanced cancers. The goal is to assess the long-term safety and effectiveness of this treatment. The trial is open to individuals who participated in previous pembrolizumab studies and are either still receiving the treatment or are in a follow-up phase. Participants must not have received any other cancer treatment since their last dose of pembrolizumab. As a Phase 3 trial, this study serves as the final step before potential FDA approval, offering participants the opportunity to contribute to the validation of a promising treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or other immunosuppressive treatments, you may need to stop them before starting the trial.

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

Research has shown that pembrolizumab is generally well-tolerated by patients. About 74.3% of patients experienced some side effects, but most were manageable, with serious side effects being less common.

For lenvatinib, 57.8% of patients reported side effects, and 13.5% experienced severe ones, such as tiredness and high blood pressure.

Olaparib has demonstrated a consistent safety record across studies, with side effects that are usually manageable. Common issues included nausea and tiredness, but these were not severe for most patients.

Studies indicate that MK-4280 is generally safe, especially when used with pembrolizumab. Most side effects were mild, and no treatment-related deaths occurred.

Overall, while side effects can occur with these treatments, they are often manageable and not severe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab for advanced cancers because it leverages the body's immune system to target cancer cells, which is different from traditional chemotherapy that attacks both cancerous and healthy cells. Pembrolizumab is a type of immunotherapy known as a checkpoint inhibitor, specifically targeting the PD-1 pathway to help the immune system recognize and combat cancer cells more effectively. This approach can potentially lead to fewer side effects and more durable responses compared to the standard chemotherapy options. Additionally, the trial explores combinations with other drugs like lenvatinib and olaparib, which may enhance efficacy by targeting cancer through multiple mechanisms.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research has shown that pembrolizumab, a treatment for advanced cancers, yields promising results. Studies indicate that pembrolizumab improved survival rates in advanced melanoma, with over one-third of patients alive after 10 years, compared to less than a quarter with other treatments. For advanced or spreading cancers, patients lived about 5.73 months without the cancer worsening, with many surviving at 12, 24, and even 60 months.

In this trial, participants may receive Lenvatinib, often used with pembrolizumab. Studies have found a 66% response rate with Lenvatinib, with some patients experiencing complete remission, meaning their cancer was no longer detectable. Lenvatinib has also improved the time patients lived without cancer progression after other treatments failed.

Olaparib is another treatment option being studied in this trial. It has been effective in certain cancers like metastatic breast cancer, reducing the risk of cancer worsening or causing death by 42% compared to some chemotherapies. In some cases, complete responses were observed, meaning the cancer could not be found in follow-up exams. These findings highlight the potential of these treatments in fighting advanced cancers. ^{4 6 7 8 9}

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 adults with advanced tumors who were previously in a pembrolizumab study. They must not have had cancer treatment since the last dose of pembrolizumab, be relatively healthy (ECOG status 0 or 1), and women must agree to use contraception. People can't join if they have active brain metastases, certain immune conditions, severe infections like HIV or hepatitis, are pregnant/breastfeeding, or have serious heart/liver/thyroid/diabetes issues.

Inclusion Criteria

Additional eligibility criteria for participants who enter Second Course Phase once they are enrolled on MK-3475-587:

I am eligible for treatment with Lenvatinib.

My blood pressure is under 150/90 mmHg, with or without medication.

Exclusion Criteria

I have lung scarring along with my NSCLC.

I am currently being treated for an infection.

My liver is not functioning well (Child-Pugh score >6).

Timeline for a Trial Participant

First Course Phase

Participants receive up to 35 doses every 3 weeks or 17 doses every 6 weeks of pembrolizumab or a pembrolizumab-based combination or lenvatinib according to arm assignment.

Approximately 2 years

Second Course Phase

Participants complete up to 17 doses every 3 weeks or 8 doses every 6 weeks of pembrolizumab or a pembrolizumab-based combination according to arm assignment.

Approximately 1 year

Survival Follow-up Phase

Participants are monitored for survival outcomes after treatment completion.

Up to approximately 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Standard of Care (SOC)

Trial Overview The trial tests long-term safety and effectiveness of pembrolizumab for blood cancers and solid tumors. Participants from earlier studies continue with up to 35 doses every three weeks or up to 17 doses every six weeks. The study has phases depending on prior treatment: First Course Phase, Survival Follow-up Phase, or Second Course Phase.

How Is the Trial Designed?

Group I: Pembrolizumab 400 mg + SOC (Per Parent Study) Experimental Treatment 2 Interventions

Participants receive pembrolizumab 400 mg via IV infusion on Day 1 of each 6-week cycle PLUS SOC treatment (or per parent study if there is no SOC) for up to 17 administrations or more for First Course participants and up to 8 administrations for Second Course participants. Participants receiving a pembrolizumab-based combination treatment will receive the dose regimen of the combination drug(s) which is recommended per SOC or was used in the parent study protocol if there is no SOC recommendation.

Group II: Pembrolizumab 400 mg Experimental Treatment 1 Intervention

Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week cycle for up to 17 administrations or more for First Course participants and up to 8 administrations for Second Course participants.

Group III: Pembrolizumab 200 mg + SOC: Per Parent Study) Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle PLUS standard of care (SOC) treatment (or per parent study if there is no SOC) for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants. Participants receiving a pembrolizumab-based combination treatment will receive the dose regimen of the combination drug(s) which is recommended per SOC or was used in the parent study protocol if there is no SOC recommendation.

Group IV: Pembrolizumab 200 mg Experimental Treatment 1 Intervention

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations or more for First Course participants and up to 17 administrations for Second Course participants.

Group V: Olaparib 300mg Experimental Treatment 1 Intervention

Participants receive Olaparib 300 mg orally twice daily (BID) until disease progression or toxicity prohibits its administration.

Group VI: Olaparib 250mg Experimental Treatment 1 Intervention

Participants receive Olaparib 250 mg orally twice daily (BID) until disease progression or toxicity prohibits its administration.

Group VII: Olaparib 100mg Experimental Treatment 1 Intervention

Participants receive Olaparib 100 mg orally twice daily (BID) until disease progression or toxicity prohibits its administration.

Group VIII: MK-4280A Experimental Treatment 1 Intervention

Participants receive MK-4280A (800mg favezelimab + 200mg pembrolizumab) as IV infusion every 3 weeks (Q3W) and may continue study therapy until study treatment completion or may transition to pembrolizumab to complete their treatment.

Group IX: MK-4280 800mg Experimental Treatment 1 Intervention

Participants receive MK-4280 800mg as IV infusion every 3 weeks (Q3W) and may continue study therapy until study treatment completion or may transition to pembrolizumab to complete their treatment.

Group X: Lenvatinib 8 mg Experimental Treatment 1 Intervention

Participants with body weight (BW)\<60 kg receive Lenvatinib 8 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.

Group XI: Lenvatinib 2mg Experimental Treatment 1 Intervention

Participants with body weight (BW)\<60 kg receive Lenvatinib 2 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumab administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.

Group XII: Lenvatinib 24 mg Experimental Treatment 1 Intervention

Participants with body weight (BW)\>60 kg receive Lenvatinib 24 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.

Group XIII: Lenvatinib 20 mg Experimental Treatment 1 Intervention

Participants with body weight (BW)\>60kg receive Lenvatinib 20mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.

Group XIV: Lenvatinib 12 mg Experimental Treatment 1 Intervention

Participants with body weight (BW)\>60 kg receive Lenvatinib 12 mg orally once daily on a 21 or 42 day cycle. It is taken 0-4 hours after completion of pembrolizumabd administration in the clinic on cycle 1 day 1(C1D1), C2D1, C3D1, etc. Taken at home on all other days.

Group XV: SOC (Per Parent Study) Active Control 1 Intervention

Participants receive the dose matched non-pembrolizumab SOC treatment (e.g. chemotherapy) they were receiving as per parent study protocol.

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

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. 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

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) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab was found to be safe and well tolerated in a phase I study involving 20 patients with advanced solid tumors, with no dose-limiting toxicities observed at doses up to 10 mg/kg every 2 weeks.

The treatment demonstrated durable antitumor activity, with complete responses in two patients and stable disease in 15 others, indicating that a minimum effective dose for antitumor activity is 2 mg/kg every 3 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Patnaik, A., Kang, SP., Rasco, D., 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, 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 (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2949820125000311

Effectiveness, toxicity and treatment adjustments of ... The objective response rate was 66%, with 8% of patients achieving a complete remission. Primary progression was seen in 8% of patients. At a median follow-up ...

2. merck.com merck.com/news/merck-and-eisai-announce-welireg-belzutifan-plus-lenvima-lenvatinib-met-primary-endpoint-of-progression-free-survival-pfs-in-certain-previously-treated-patients-with-advanced-renal-c/

Merck and Eisai Announce WELIREG® (belzutifan) Plus ... First treatment regimen to demonstrate a statistically significant improvement in PFS for patients whose disease progressed following anti-PD-1/L1 therapy ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39504640/

Real World Outcomes in Patients With Recurrent, ... The 6-month progression-free and overall survival rates were 54.0% (95%CI: 39.0-66.8) and 70.1% (95%CI:56.5-80.1) respectively. Conclusion: This ...

4. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-kidney-cancer/164170-esmo-2025-final-analysis-of-lenvatinib-pembrolizumab-versus-sunitinib-in-patients-with-advanced-rcc-with-or-without-bone-metastases-in-clear.html

ESMO 2025: Final Analysis of Lenvatinib + Pembrolizumab ... Improved efficacy with lenvatinib + pembrolizumab continued to be observed after ~4 years of follow-up (data cutoff: 31 July 2022):. As such, at ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9032633/

Lenvatinib Therapy for Advanced Thyroid Cancer Efficacy outcomes are summarized in Table 2. The BOR was PR in 10 patients (37.0%), stable disease in 13 patients (48.1%), and PD in 1 patient (3.7%). No ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11572195/

Real-world safety and effectiveness of lenvatinib in ... Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia ...

7. lenvima.com lenvima.com/-/media/Project/EISAI/Lenvima/PDF/prescribing-information.pdf

Prescribing Information Safety data obtained in 1823 patients with advanced solid tumors who received LENVIMA as a single agent across multiple clinical studies was used to further ...

8. keytrudalenvimahcp.com keytrudalenvimahcp.com/advanced-renal-cell-carcinoma/

Advanced Renal Cell Carcinoma: Efficacy and Safety Results Serious adverse reactions occurred in 51% of patients; the most common (≥2%) were hemorrhagic events (5%), diarrhea (4%), hypertension, myocardial infarction, ...

9. aacrjournals.org aacrjournals.org/clincancerres/article/22/6/1385/122036/Safety-and-Pharmacokinetics-of-Lenvatinib-in

Safety and Pharmacokinetics of Lenvatinib in Patients with ... Lenvatinib has shown promising antitumor efficacy in advanced solid tumors (16, 17, 19, 20). Preliminary studies suggested the use of up to 25 mg once daily ...