Pembrolizumab for Lung Cancer

Overseen By Anahid Aminpour

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Systemic steroids, Immunosuppressives

Disqualifiers: Transplant history, Active autoimmune, 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: Unknown

Duration: Up to 36 months

318 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of pembrolizumab (also known as KEYTRUDA, an immunotherapy drug) in treating advanced lung cancer in Black patients. Participants will receive pembrolizumab, either alone or with chemotherapy, based on their specific cancer characteristics. The trial seeks Black adults with advanced non-small cell lung cancer (NSCLC) who do not have certain mutations in their tumors. Suitable candidates may have been recently diagnosed or have recurrent disease at least six months after previous treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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 systemic steroid therapy at doses of 10 mg prednisone or higher, you may not be eligible to participate.

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

Research shows that pembrolizumab, used alone or with chemotherapy, is generally safe for treating lung cancer. Studies found that patients using pembrolizumab alone had a five-year survival rate of 11.9%. Those who used pembrolizumab with chemotherapy had survival rates of 19.4% and 18.4% in different studies.

Pembrolizumab has been well-tolerated in various trials, though some patients may experience side effects ranging from mild to severe. The overall safety record supports its continued use and study in clinical settings. Potential risks and benefits should always be discussed with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Pembrolizumab is unique because it harnesses the power of the immune system to target lung cancer cells. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, pembrolizumab specifically blocks the PD-1 pathway, helping the immune system recognize and destroy cancer cells more effectively. Researchers are particularly excited about its potential to be used in combination with chemotherapy, as well as its ability to work as a monotherapy in patients with specific tumor markers like PD-L1. This targeted approach might offer more personalized and effective treatment options for patients with non-small cell lung cancer (NSCLC), potentially improving outcomes and reducing side effects compared to conventional therapies.

What is the effectiveness track record for pembrolizumab in treating lung cancer?

Research has shown that pembrolizumab effectively treats non-small cell lung cancer (NSCLC). In this trial, participants in Cohort 2 Arm A will receive pembrolizumab monotherapy. Studies indicate that pembrolizumab alone can lead to a 5-year survival rate of up to 22%, meaning about 22% of patients remain alive five years after starting treatment. Participants in Cohort 2 Arm B will receive a combination of chemotherapy and pembrolizumab. This combination has reduced the risk of cancer spreading or worsening by 48% compared to chemotherapy alone, with 5-year survival rates of around 19% to 18% in different studies, supporting its use as a strong treatment option for NSCLC. ^{3 6 7 8 9}

Who Is on the Research Team?

Jhanelle E. Gray, M.D.

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for Black patients with advanced or metastatic non-small cell lung cancer (NSCLC) without specific genetic mutations. Participants must be adults, have a performance status showing they can carry out daily activities, and may have detectable circulating tumor DNA.

Inclusion Criteria

I have not received any treatment for my advanced or recurrent cancer.

Be Black / African American per self-report

My cancer does not have EGFR, ALK, or ROS1 mutations.

Exclusion Criteria

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, that would substantially increase the risk of incurring adverse events (AEs) from the study medications, that would interfere with the subject's participation for the full duration of the study or is not in the best interest of the subject to participate, in the opinion of the treating investigator

I have brain metastases but am stable and haven't needed high-dose steroids recently.

History of allogenic tissue/solid organ transplant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab with or without chemotherapy based on cohort assignment

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests how well Black patients respond to a combination of chemotherapy drugs (Carboplatin, Cisplatin, Paclitaxel, Pemetrexed) and the immunotherapy drug Pembrolizumab. Some may also receive Abraxane as part of their treatment regimen.

How Is the Trial Designed?

Group I: Cohort 2: arm B Experimental Treatment 6 Interventions

Cohort 2 Arm B will enroll patients with NSCLC with any PD-L1 status and ctDNAtumor fraction intermediate/high -OR- PD-L1 TPS\<1% and any ctDNA level treated with chemotherapy plus pembrolizumab.

Group II: Cohort 2: arm A Experimental Treatment 1 Intervention

Cohort 2 Arm A will enroll patients with NSCLC with PD-L1 TPS status ≥1% and ctDNA tumor fraction low/negative and be treated with pembrolizumab monotherapy.

Group III: Cohort 1 Experimental Treatment 6 Interventions

Non-interventional prospective cohort and participants will receive standard of care pembrolizumab with or without chemotherapy.

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Merck Sharp & Dohme LLC

Industry 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

Foundation Medicine

Industry Sponsor

Trials

37

Recruited

17,600+

Go-2 Lung

Collaborator

Trials

1

Recruited

320+

Published Research Related to This Trial

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]

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]

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]

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 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 (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]

Citations

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KEYTRUDA® (pembrolizumab) Demonstrates Long-Term ... “The five-year benefit demonstrated across overall survival and event-free survival from KEYNOTE-671 supports the continued use of this ...

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5-Year Real-World Outcomes With Frontline ... Median OS was 19.2 months (95% CI, 16.6-21.4), and survival rate at 5 years was 25.1% (95% CI, 21.7-28.7). Overall, 266 patients (33 ...

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

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 ...

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

Non–Small Cell Lung Cancer - Clinical Trial Results KEYTRUDA may be used alone as a treatment in adults for your lung cancer to help prevent your lung cancer from coming back after your tumor(s) has been removed ...

5. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%). In KEYNOTE⁠-⁠671, adverse reactions ...

6. 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.

7. 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.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

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

Real-world evidence for pembrolizumab in non-small cell ... Median survival increased from about 8 months (between 7.6 and 8.6 months) for patients treated with advanced SACT in the pre-ICI era to 10.0 ...