Pembrolizumab for Lung Cancer

Recruiting at 5 trial locations

Overseen By Janet Dancey

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Canadian Cancer Trials Group

Must be taking: Pembrolizumab

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Symptomatic CNS metastases, Active infection, Autoimmune disease, others

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

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: 1

Duration: 6 weeks

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of pembrolizumab, an immunotherapy drug, for treating non-small cell lung cancer. The researchers aim to determine if adjusting treatment based on ctDNA (tiny bits of cancer DNA found in the blood) can improve outcomes. Participants will receive either pembrolizumab alone or in combination with standard chemotherapy. Suitable candidates have been diagnosed with metastatic non-small cell lung cancer, tested negative for certain mutations, and have high levels of the protein PD-L1 in their tumors. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on other anti-cancer therapies or investigational anti-cancer agents while participating in this trial.

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

Research has shown that pembrolizumab, used alone or with platinum-based chemotherapy, has been safe in previous studies. Specifically, studies found that 11.9% of patients with non-small cell lung cancer survived for five years with pembrolizumab alone, and it continues to perform well over time. Many patients have tolerated this treatment well.

When combined with platinum-based chemotherapy, pembrolizumab maintains similar safety. Different studies reported five-year survival rates of 19.4% and 18.4%, indicating better outcomes than chemotherapy alone. These results suggest that the combination is also well-tolerated.

Overall, pembrolizumab, whether used alone or with chemotherapy, has shown safety and effectiveness over long periods. While side effects can occur, many patients have managed them well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Pembrolizumab is unique because it harnesses the body's immune system to fight lung cancer by targeting the PD-1 pathway. This mechanism differs from traditional chemotherapy, which generally attacks rapidly dividing cells. Researchers are excited because Pembrolizumab can potentially lead to more precise and less toxic treatment options. Additionally, when combined with standard platinum-based chemotherapy, it might offer enhanced effectiveness, providing hope for better outcomes compared to standard treatments alone.

What is the effectiveness track record for Pembrolizumab in treating non-small cell lung cancer?

Research has shown that pembrolizumab, one of the treatments in this trial, holds promise for treating non-small cell lung cancer (NSCLC) when used alone. Data over five years indicates that patients have a survival rate of up to 22% with pembrolizumab alone, suggesting it could significantly improve long-term survival for some patients.

In this trial, another group of participants will receive pembrolizumab combined with platinum-based chemotherapy. Studies have found that this combination leads to better response rates and longer periods without cancer worsening compared to chemotherapy alone. Specifically, two major studies reported five-year overall survival rates of about 19.4% and 18.4%. This combination appears to enhance treatment effectiveness for advanced NSCLC. ^{1 4 6 7 8}

Who Is on the Research Team?

Sara Moore

Principal Investigator

Ottawa Hospital Research Institute

Valsamo Anagnostou

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Adults with metastatic Non-Small Cell Lung Cancer (NSCLC) who haven't had systemic chemotherapy or immunotherapy for advanced cancer. They must have a PD-L1 expression score of at least 1%, be in good physical condition, and agree to use effective contraception. Not eligible if they've had certain other cancers, are pregnant, have untreated brain metastases requiring steroids, or conditions that pembrolizumab could worsen.

Inclusion Criteria

Patients must consent to collection of liquid biopsy (blood) samples for ctDNA analysis by CLIA central laboratory and for correlative analysis by a research central laboratory.

Women/men of childbearing potential must have agreed to use a highly effective contraceptive method. Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation.

Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, collection of blood samples, response assessments and follow-up. Patients must agree to return to their primary care facility for response assessments as well as any adverse events which may occur through the course of the trial.

Exclusion Criteria

I cannot take pembrolizumab due to an active infection, autoimmune disease, need for immunosuppressants, severe immune reactions, or allergy to it.

I am not currently receiving any other cancer treatments.

I had cancer before, but it won't affect this trial's treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab alone or pembrolizumab with standard platinum-based chemotherapy based on ctDNA response

6 weeks

1 visit (in-person) for liquid biopsy

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial is testing whether blood tests can effectively monitor the response to pembrolizumab treatment in NSCLC patients. Pembrolizumab is an immunotherapy drug designed to help the body's immune system fight cancer cells.

How Is the Trial Designed?

Group I: Pembrolizumab + standard platinum-based chemotherapy Experimental Treatment 1 Intervention

Per current Product Monograph/U.S. Drug Label and/or local guidelines.

Group II: Pembrolizumab alone Active Control 1 Intervention

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?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Personal Genome Diagnostics

Industry Sponsor

Trials

4

Recruited

1,700+

Mark Foundation for Cancer Research

Collaborator

Trials

1

Recruited

230+

Cancer Research Institute, New York City

Collaborator

Trials

22

Recruited

1,300+

Personal Genome Diagnostics (PGDx)

Collaborator

Trials

2

Recruited

1,600+

Published Research Related to This Trial

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, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

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 (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, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

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]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10082298/

Five-Year Outcomes With Pembrolizumab Versus ... With 5-year OS rates of up to 22%, these data support the continued use of pembrolizumab monotherapy as a standard-of-care treatment for previously untreated PD ...

2. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

3. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(24)00081-0/fulltext

5-Year Real-World Outcomes With Frontline ... With 5-year follow-up in a real-world population, frontline pembrolizumab monotherapy continues to demonstrate long-term effectiveness.

4. nature.com nature.com/articles/s41416-024-02895-1

Real-world evidence for pembrolizumab in non-small cell ... Median OS of patients treated with 1 L pembrolizumab after 2017 was better (mono-/combination therapy: 13.8/12.8 months) than for patients ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0169500225000431

Five-year efficacy and safety of pembrolizumab as first-line ... The real-world 5-year survival rate of NSCLC cases with PD-L1 ≥ 50 % treated with first-line pembrolizumab was comparable to that in a clinical trial.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39952082/

Five-year efficacy and safety of pembrolizumab as first-line ... The real-world 5-year survival rate of NSCLC cases with PD-L1 ≥ 50 % treated with first-line pembrolizumab was comparable to that in a clinical trial.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02885

Five-Year Outcomes With Pembrolizumab Versus ... The estimated 5-year OS rates were 11.9% and 7.4% in the pembrolizumab and chemotherapy groups, respectively (Data Supplement). Safety. In the ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02142738

NCT02142738 | Study of Pembrolizumab (MK-3475) ... This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies.