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

Trial Summary

What is the purpose of this trial?

This single center open-label trial will enroll a single cohort of patients with advanced non-small cell lung cancer (NSCLC) who are ineligible for treatment with curative intent due to 1) disease stage IV, or 2) inability to tolerate intensive surgery or chemo-radiation. Patients will be eligible for the trial if ISMMS reviewed samples from tumor biopsy have a PDL-1 TPS ≥ 1% and have ECOG performance status rated 2 or 3. All patients will receive anti PD-1 therapy with pembrolizumab 200mg IV every 3 weeks, during which patients will also undergo serial QOL assessments. This trial will follow a phase II single arm, open label design. The study will enroll 45 patients evaluable for the primary endpoint of which will be change in QOL as measured by the EORTC's QLQ-C30 between Day 1 and Day 84 +/- 7 days. Secondary outcomes including evaluation for development of confounding mental health conditions will be evaluated via serial HADS assessments. Concomitant radiographic assessment with PET/CT, regardless of the doses of pembrolizumab received, will allow for evaluation of secondary efficacy outcomes, including disease response by RECIST 1.1 criteria.

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.

What data supports the effectiveness of the drug pembrolizumab for advanced non-small cell lung cancer?

Research shows that pembrolizumab helps patients with advanced non-small cell lung cancer live longer and slows down the progression of the disease. It is especially effective for tumors with high levels of a protein called PD-L1. ^{1 2 3 4 5}

Is pembrolizumab safe for humans?

Pembrolizumab (also known as Keytruda or MK-3475) has been used in clinical trials for various cancers, including lung cancer and melanoma. Common side effects include fatigue, cough, nausea, and rash, while more serious immune-related side effects can include lung inflammation (pneumonitis), liver inflammation (hepatitis), and thyroid problems. These side effects are generally considered manageable, and the benefits of treatment often outweigh the risks for serious conditions. ^{1 2 3 6 7}

What makes the drug pembrolizumab unique for treating advanced non-small cell lung cancer?

Pembrolizumab is unique because it is an immune checkpoint inhibitor that targets the PD-1/PD-L1 pathway, helping the immune system recognize and attack cancer cells. It is approved for patients with tumors expressing PD-L1 and has shown significant improvements in survival compared to traditional chemotherapy. ^{1 2 3 5 8}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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]

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]

References

1. 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]

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

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

3. 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]

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

Pembrolizumab Shows Promise for NSCLC. [2015]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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