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

Recruiting at 228 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of two treatments for metastatic non-small cell lung cancer (NSCLC). It compares the use of pembrolizumab, an immunotherapy drug, alone versus in combination with sacituzumab govitecan, an antibody-drug conjugate, to determine which option prolongs life without cancer progression. Suitable candidates for this trial have NSCLC that has spread to other parts of the body and a specific marker (PD-L1) in at least 50% of their tumor cells. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients access to potentially groundbreaking 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.

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

Research has shown that pembrolizumab is generally well-tolerated by people with non-small cell lung cancer (NSCLC). One study found that patients had a 5-year survival rate similar to those in clinical trials, indicating consistent safety results. Some side effects have been noted, but they are usually manageable.

For the combination of pembrolizumab and sacituzumab govitecan, early research appears promising. Data from the EVOKE-02 study suggested that this combination works well and is generally safe. Patients experienced longer periods where their cancer did not worsen compared to other treatments. While some side effects occurred, they were mostly typical of cancer treatments.

Overall, both treatments have demonstrated a reasonable safety profile in studies, though specific side effects can vary. Clinical trial participants will be closely monitored to manage any adverse effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they offer a novel combination of therapies that may enhance treatment efficacy. Pembrolizumab is already a well-known immunotherapy that helps the immune system target cancer cells. The addition of sacituzumab govitecan, an antibody-drug conjugate, is unique because it delivers a potent chemotherapy directly to the cancer cells, potentially reducing harm to healthy cells and improving outcomes. This combination could provide a more targeted approach compared to traditional chemotherapy and immunotherapy alone.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that pembrolizumab (Keytruda) can extend the lives of patients with non-small cell lung cancer (NSCLC), particularly when tumors have a PD-L1 score of 50% or higher. In this trial, participants will receive either pembrolizumab alone or in combination with sacituzumab govitecan (Trodelvy). Studies have found that adding pembrolizumab to chemotherapy improves patient response and delays cancer progression compared to chemotherapy alone. Specifically, combining pembrolizumab with sacituzumab govitecan has reduced the risk of cancer progression or death by 35% compared to pembrolizumab with chemotherapy alone. This combination has shown promise as an initial treatment for advanced NSCLC. These findings suggest that these treatments, whether used alone or together, could effectively manage this type of lung cancer. ^{2 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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]

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]

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 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 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]

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]

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, 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]

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]

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]

Citations

1. 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.

2. 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.

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

Real-world evidence for pembrolizumab in non-small cell ... Our nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02142738

NCT02142738 | Study of Pembrolizumab (MK-3475) ... This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03425643

NCT03425643 | Efficacy and Safety of Pembrolizumab (MK ... This trial will evaluate the safety and efficacy of pembrolizumab (MK-3475) in combination with platinum doublet neoadjuvant chemotherapy (NAC) before surgery.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01990

5-Year Update of the Phase III KEYNOTE-407 Study We report 5-year efficacy and safety outcomes from the phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435). Eligible ...