Pembrolizumab vs. Pembrolizumab + Sacituzumab Govitecan for Non-Small Cell Lung Cancer

Recruiting at 171 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Topoisomerase inhibitors, Trop-2 therapy

Disqualifiers: Second malignancy, Cardiac disease, Autoimmune, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 48 months

614 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares pembrolizumab alone and in combination with sacituzumab govitecan in adults with advanced lung cancer who have high levels of a certain protein. Pembrolizumab boosts the immune system to fight cancer, while sacituzumab govitecan targets and kills cancer cells. Pembrolizumab has been used as a standard treatment for a type of lung cancer, showing improved survival rates compared to other treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop these at least 7 days before starting the study medication.

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

Pembrolizumab has shown effectiveness in treating non-small cell lung cancer, especially in patients with high levels of PD-L1, a protein that helps cancer cells hide from the immune system. Studies have demonstrated its success in both early and advanced stages of the disease, often outperforming traditional chemotherapy. ^{1 2 3 4 5}

What safety data exists for Pembrolizumab and Sacituzumab Govitecan in humans?

Pembrolizumab has been studied in various trials for non-small cell lung cancer and other cancers, showing it generally has fewer treatment-related side effects compared to chemotherapy. Sacituzumab Govitecan's safety profile is not detailed in the provided research, but Pembrolizumab alone has been evaluated for safety in multiple studies. ^{3 4 6 7 8}

What makes the drug combination of Pembrolizumab and Sacituzumab Govitecan unique for treating non-small cell lung cancer?

This drug combination is unique because it combines Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with Sacituzumab Govitecan, an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, potentially enhancing the treatment's effectiveness compared to using Pembrolizumab alone. ^{3 6 9 10 11}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer showing high levels of PD-L1. Participants must not have had previous cancer treatments, have a life expectancy over 3 months, and cannot be eligible for EGFR or ALK-1 targeted therapy. They should not have serious heart conditions, active infections, certain viral hepatitis histories, recent vaccinations with live viruses, autoimmune diseases needing treatment in the last 2 years, or severe allergies to the drugs being tested.

Inclusion Criteria

My lung cancer is confirmed to be non-small cell type and has spread.

You are expected to live for at least 3 more months.

My cancer is not suitable for treatments targeting EGFR, ALK-1, or ROS-1.

Exclusion Criteria

I have not had a live vaccine in the last 30 days.

I have been treated with specific immune therapy for cancer.

Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab with or without sacituzumab govitecan in 21-day cycles until progression or unacceptable toxicity

Up to 48 months

IV infusions on Day 1 and Day 8 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Pembrolizumab
• Sacituzumab Govitecan

Trial Overview The study compares two approaches: one group receives Pembrolizumab alone while another gets a combination of Pembrolizumab and Sacituzumab Govitecan. The main focus is on how long patients live without their disease getting worse (PFS) and overall survival (OS), assessed by independent reviewers using standard criteria.

Participant Groups

Group I: Pembrolizumab + Sacituzumab Govitecan Experimental Treatment 2 Interventions

Participants receive sacituzumab govitecan 10mg/kg intravenous (IV) infusion once weekly on Day 1 and Day 8 of a continuous 21-day cycle until progressive disease (PD) requiring discontinuation, unacceptable toxicity, withdrawal of consent, or death. Participants receive pembrolizumab 200mg IV infusion on Day 1 every 3 weeks (Q3W) for up to 35 cycles (each cycle length = 21 days).

Group II: Pembrolizumab Experimental Treatment 1 Intervention

Participants receive pembrolizumab 200mg IV infusion on Day 1 Q3W for up to 35 cycles (each cycle length = 21 days).

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?

Merck Sharp & Dohme LLC

Lead 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

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant efficacy in treating advanced non-small-cell lung cancer (NSCLC) across multiple clinical trials, particularly in patients with PD-L1 expression levels of 1% or higher.

The KEYNOTE studies identified specific patient populations that benefit most from pembrolizumab, highlighting the importance of PD-L1 as a companion diagnostic, while future research will explore its role in earlier stages of cancer treatment and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. Palumbo, G., Carillio, G., Manzo, A., 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]

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 study of 145 patients with PD-L1 strongly positive non-small-cell lung cancer (NSCLC), those with higher PD-L1 expression (≥ 75%) experienced better treatment outcomes with pembrolizumab, showing a higher objective response rate (51% vs. 33%) and longer progression-free survival (13.9 months vs. 5.2 months).

Patients with liver metastasis had significantly poorer responses to pembrolizumab, with an objective response rate of only 20% compared to 47% in those without liver metastasis, indicating that both PD-L1 expression and liver metastasis are important predictors of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. Takeyasu, Y., Yoshida, T., Shibaki, R., et al.[2021]

In a multicenter observational study involving 300 patients with non-small cell lung cancer (NSCLC), pembrolizumab demonstrated a median overall survival of 558 days and a progression-free survival of 188 days, indicating its efficacy in real-world settings.

The study confirmed that factors such as performance status and PD-L1 expression significantly influenced overall survival, while the toxicity profile of pembrolizumab remained consistent with previous reports, suggesting it is a safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data. Terai, H., Soejima, K., Shimokawa, A., et al.[2022]

Pembrolizumab monotherapy significantly improved quality-adjusted survival (Q-TWiST) by 2.49 months compared to platinum-based chemotherapy and by 2.29 months compared to docetaxel in patients with advanced non-small cell lung cancer, indicating its efficacy in enhancing patient quality of life.

The benefits of pembrolizumab continued to increase over time, suggesting that it not only offers longer overall survival but also fewer treatment-related adverse events compared to traditional chemotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer. Huang, M., Pietanza, MC., Samkari, A., et al.[2020]

In a phase 1 study involving Japanese patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab combined with chemotherapy demonstrated a feasible safety profile, with only one dose-limiting toxicity reported in part B and two in part C, indicating that this treatment can be safely administered.

The overall response rates were promising, with 73% in the nonsquamous group and 50% in the squamous group, showing significant antitumor activity regardless of PD-L1 status, which aligns with findings from international trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC. Kurata, T., Nakagawa, K., Satouchi, M., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., 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. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. [2020]

2. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [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. England pubmed.ncbi.nlm.nih.gov

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

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

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. [2021]

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

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC. [2022]

9. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

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

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

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