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

Trial Summary

What is the purpose of this trial?

BR36 will evaluate the potential clinical benefit of tailoring immunotherapy treatment based on ctDNA molecular response in non-small cell lung cancer.

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.

What data supports the effectiveness of the drug pembrolizumab for lung cancer?

Pembrolizumab has been shown to improve survival in patients with metastatic non-small cell lung cancer, especially those whose tumors express a protein called PD-L1. In clinical trials, patients treated with pembrolizumab lived longer and had a longer time before their cancer got worse compared to those who received chemotherapy. ^{1 2 3 4 5}

Is pembrolizumab safe for humans?

Pembrolizumab (also known as Keytruda or MK-3475) has been studied for safety in various conditions, including lung cancer and melanoma. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects can include pneumonitis (lung inflammation), colitis (inflammation of the colon), and thyroid disorders. These side effects are generally considered manageable, and the benefits of treatment often outweigh the risks in serious conditions. ^{1 2 5 6 7}

How is the drug pembrolizumab unique for treating lung cancer?

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, and it has shown better survival outcomes compared to traditional chemotherapy for non-small cell lung cancer. ^{1 2 3 8 9}

Research Team

Sara Moore

Principal Investigator

Ottawa Hospital Research Institute

Valsamo Anagnostou

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 (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, 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, 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, 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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

8. Germany pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]