Pembrolizumab for Advanced Cancers

Recruiting at 692 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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the long-term safety and efficacy of pembrolizumab (MK-3475) in participants from previous Merck pembrolizumab-based parent studies who transition into this extension study. This study will consist of three phases: 1) First Course Phase, 2) Survival Follow-up Phase or 3) Second Course Phase. Each participant will transition to this extension study in one of the following three phases, depending on the study phase they were in at the completion of the parent study. Participants who were in the First Course Phase of study treatment with pembrolizumab or lenvatinib in their parent study will enter the First Course Phase of this study and complete up to 35 doses or more every 3 weeks (Q3W) or 17 doses or more every 6 weeks (Q6W) of study treatment with pembrolizumab or a pembrolizumab-based combination or lenvatinib according to arm assignment. Participants who were in the Follow-up Phase in the parent study (post-treatment or Survival Follow-up Phase) will enter the Survival Follow-up Phase of this study. Participants who were in the Second Course Phase in their parent study will enter Second Course Phase of this study and complete up to 17 doses Q3W or 8 doses Q6W of study treatment with pembrolizumab or a pembrolizumab-based combination according to arm assignment. Any participant originating from a parent trial where crossover to pembrolizumab was permitted upon disease progression may be eligible for 35 doses as Q3W or 17 doses Q6W of pembrolizumab (approximately 2 years), if they progress while on the control arm and pembrolizumab is approved for the indication in the country where the potential eligible crossover participant is being evaluated.

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.

What data supports the effectiveness of the drug pembrolizumab for advanced cancers?

Pembrolizumab has shown effectiveness in treating advanced cancers like non-small cell lung cancer and melanoma by improving survival rates and slowing disease progression. It works by helping the immune system attack cancer cells, and has been approved for use in certain types of lung cancer and melanoma based on clinical trials demonstrating these benefits. ^{1 2 3 4 5}

Is pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been approved by the FDA for certain cancers and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related issues like inflammation of the lungs, liver, or thyroid. Rarely, it can lead to type 1 diabetes. Always discuss potential risks with your doctor. ^{3 4 5 6 7}

How is the drug pembrolizumab unique for treating advanced cancers?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that targets the PD-1 pathway, helping the immune system recognize and attack cancer cells. Unlike traditional chemotherapy, it is designed to be more effective and less toxic, although it can have side effects like pneumonitis (lung inflammation). ^{3 4 5 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 (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]

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]

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, 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]

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]

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, 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]

References

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

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. [2022]

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

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

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

8. China 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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