Pembrolizumab for Advanced Non-Small Cell Lung Cancer

Overseen By Deborah Doroshow, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: Anti PD-1 therapy

Must not be taking: Systemic immunosuppressive therapy

Disqualifiers: Autoimmune conditions, Uncontrolled illness, 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: 6

Duration: 12 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, an immunotherapy drug, to improve the quality of life for people with advanced non-small cell lung cancer (NSCLC) who cannot undergo surgery or chemotherapy due to the cancer's advanced stage or other health reasons. Participants will receive the drug every three weeks, with progress monitored through health checkups and scans. People with NSCLC who have not received other cancer treatments and can manage light daily activities might be suitable candidates. The trial aims to determine if pembrolizumab can enhance daily living for these patients over a 12-week period. As a Phase 2 trial, this research measures how well pembrolizumab works in an initial, smaller group, offering a chance to potentially improve quality of life.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications for autoimmune conditions requiring more than 10mg of prednisone daily or other systemic immunosuppressive therapy, you may not be eligible to participate.

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

Research has shown that pembrolizumab, also known as Keytruda, is consistently safe across various cancer types. Studies have found it to be generally well-tolerated by patients with advanced non-small cell lung cancer. Most side effects are manageable and similar to those seen with other advanced diseases. The FDA has already approved the treatment for certain patients with advanced non-small cell lung cancer, offering reassurance about its safety. While every treatment can have side effects, pembrolizumab is considered a safe option for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it works by targeting the PD-1 pathway, which helps the immune system recognize and attack cancer cells more effectively. Unlike traditional chemotherapy that attacks rapidly dividing cells indiscriminately, pembrolizumab specifically enhances the body's immune response against tumor cells. Researchers are excited about pembrolizumab because it offers a more targeted approach with the potential for fewer side effects, and it can be given less frequently over time, transitioning from every three weeks to every six weeks for suitable patients.

What evidence suggests that pembrolizumab might be an effective treatment for advanced non-small cell lung cancer?

Research has shown that pembrolizumab can help treat advanced non-small cell lung cancer (NSCLC), particularly in patients with high levels of the protein PD-L1, which is linked to cancer growth. The KEYNOTE-024 study found that pembrolizumab led to better outcomes than standard chemotherapy for patients with PD-L1 levels of 50% or higher. Additional research has demonstrated that combining pembrolizumab with chemotherapy improved survival rates and tumor response compared to chemotherapy alone. For patients with advanced NSCLC, pembrolizumab has resulted in longer overall survival and better disease control, making it a promising treatment option. Participants in this trial will receive pembrolizumab as the investigational treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Deborah Doroshow, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Bailey Fitzgerald, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer (NSCLC) who can't have surgery or intense treatment, and haven't had systemic therapy for metastatic cancer. They must have a certain level of tumor protein (PDL-1 TPS ≥ 1%) and be physically able to take part in the study despite having an ECOG performance status of 2 or 3. Participants need functioning organs, controlled HIV if present, no recent brain metastases needing immediate treatment, and agree to use effective contraception.

Inclusion Criteria

I am a woman who can have children and have a recent negative pregnancy test.

I am HIV positive, on treatment, and my viral load is undetectable.

My doctor says I don't need immediate brain treatment for my cancer.

Exclusion Criteria

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

I need treatment for cancer that has spread to the lining of my brain and spinal cord.

I take more than 10mg of prednisone daily for an autoimmune condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200mg IV every 3 weeks for 12 weeks, with serial QOL assessments

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including QOL assessments and radiographic evaluations

12 weeks

2 visits (in-person)

Open-label extension (optional)

Participants may transition to pembrolizumab 400mg IV every 6 weeks until disease progression or unacceptable toxicity

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial is testing Pembrolizumab, an anti PD-1 therapy given intravenously every three weeks to patients with NSCLC. The main goal is to see how it affects quality of life over time using the QLQ-C30 questionnaire. Secondary goals include checking mental health changes and disease response through PET/CT scans following RECIST criteria.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

Patients will be treated with the standard dose of pembrolizumab (200mg IV every 3 weeks) for the first 12 weeks of the study. After week 12 assessments, patients without objective progression of disease are eligible to transition to Q6W dosing of pembrolizumab 400mg IV.

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?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

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 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]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8636217/

The 5‐year outcomes of the KEYNOTE‐024 trial Pembrolizumab monotherapy could provide meaningful improved patient outcomes over platinum‐based chemotherapy for advanced NSCLC patients with PD‐L1 TPS ≥ 50%.

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. keytruda.com keytruda.com/non-small-cell-lung-cancer/clinical-trial-results/

Non–Small Cell Lung Cancer - Clinical Trial Results View the clinical trial results for this treatment option for certain people with non–small cell lung cancer.

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

Five-Year Outcomes With Pembrolizumab Versus ... KEYNOTE-042 is a randomized phase III study that showed significantly longer overall survival (OS) with pembrolizumab monotherapy versus platinum-based ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1801005

Pembrolizumab plus Chemotherapy in Metastatic Non– ... The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone ...

6. 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.

7. merck.com merck.com/news/mercks-keytruda-pembrolizumab-demonstrates-superior-progression-free-and-overall-survival-compared-to-chemotherapy-as-first-line-treatment-in-patients-with-advanced-non-small-cel/

Merck's KEYTRUDA® (pembrolizumab) Demonstrates ... KEYTRUDA was superior compared to chemotherapy for both the primary endpoint of progression-free survival (PFS), and the secondary endpoint of overall survival ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1501824

Pembrolizumab for the Treatment of Non–Small-Cell Lung ... Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non–small-cell lung cancer.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38838446/

Safety of pembrolizumab as adjuvant therapy in a pooled ... Conclusions: Adjuvant pembrolizumab demonstrated a manageable safety profile that was comparable to prior reports in advanced disease. Keywords: Carcinoma, non– ...

10. keytruda.com keytruda.com/non-small-cell-lung-cancer/treatment-options/advanced-nsclc/

Advanced Non–Small Cell Lung Cancer - Treatment Option KEYTRUDA is the #1 prescribed immunotherapy in advanced NSCLC*. Learn more about the FDA-approved uses for KEYTRUDA for certain people with advanced NSCLC ...