SBRT + Pembrolizumab for Lung Cancer

No longer recruiting at 244 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

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: Unknown

Duration: up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of a targeted radiation therapy, stereotactic body radiotherapy (SBRT), with an immune-boosting drug, pembrolizumab (also known as KEYTRUDA or MK-3475). It targets individuals with early-stage non-small cell lung cancer (NSCLC) that cannot be surgically removed. The trial aims to determine if this combination improves survival without cancer progression, compared to radiation alone. Individuals with newly diagnosed NSCLC who cannot undergo surgery due to other health conditions might be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or immunosuppressive therapy, you may need to stop or adjust these medications before starting the trial.

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

Research has shown that using SBRT, a precise type of radiation therapy, with pembrolizumab, a kind of immunotherapy, is generally safe. Most patients tolerate this combination well, though some might experience side effects. For instance, there is a chance of lung inflammation, known as pneumonitis, so doctors may need to monitor patients closely.

One study found that adding pembrolizumab to SBRT did not significantly improve survival rates, but it also did not raise major safety concerns. The FDA has already approved pembrolizumab for other uses, indicating a known safety record. Overall, while some side effects can occur, the treatment is considered safe enough for further research in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Researchers are excited about SBRT combined with pembrolizumab for lung cancer because this combo offers a fresh approach to tackling tumors. Pembrolizumab is an immunotherapy that boosts the body's own immune system to attack cancer cells, unlike traditional chemotherapy that directly kills cancer cells but can also harm healthy ones. Meanwhile, SBRT delivers highly focused radiation in fewer sessions, potentially reducing side effects and making treatment more convenient. Together, they may enhance the effectiveness of treatment by shrinking tumors faster and more precisely, offering hope for improved outcomes.

What evidence suggests that SBRT plus pembrolizumab could be an effective treatment for non-small cell lung cancer?

This trial will compare the combination of pembrolizumab with stereotactic body radiotherapy (SBRT) to SBRT with a placebo. Research has shown that pembrolizumab with SBRT might enhance the immune system's ability to combat non-small cell lung cancer (NSCLC). This combination aids immune cells in recognizing and attacking cancer cells more effectively. Early results suggest this method could benefit patients whose tumors lack the PD-L1 protein, potentially extending periods without cancer progression. However, some studies found that adding pembrolizumab to SBRT did not significantly improve survival rates compared to SBRT alone. This indicates that while the treatment shows promise, its effectiveness can vary based on individual patient and tumor differences. ^{1 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

Adults with untreated Stage I or II non-small cell lung cancer (NSCLC) who can't have surgery, are eligible for SBRT, and have good organ function. Participants must agree to contraception if of childbearing potential. Exclusions include active infections, HIV, prior immunotherapy treatments, recent live vaccines, certain autoimmune diseases, pregnancy/breastfeeding, and a history of other cancers within 3 years.

Inclusion Criteria

My lung cancer is in the early stages and has not been treated yet.

I can take care of myself and am up and about more than half of my waking hours.

I can undergo SBRT and my tumor is not in the very center of my chest.

Exclusion Criteria

Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention administration

I have received an organ or tissue transplant from another person.

I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SBRT once every 3 days for 3, 4, 5, or 8 fractions over approximately 2 weeks, plus pembrolizumab or placebo every 3 weeks for up to 17 cycles (up to approximately 1 year)

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 24 weeks

Long-term Follow-up

Participants are monitored for overall survival and adverse events

up to approximately 66 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Placebo
• Stereotactic Body Radiotherapy (SBRT)

Trial Overview The trial is testing the effectiveness and safety of combining Stereotactic Body Radiotherapy (SBRT) with Pembrolizumab versus SBRT with a placebo in treating NSCLC. It aims to see if adding Pembrolizumab improves event-free survival (EFS) and overall survival (OS).

How Is the Trial Designed?

Group I: SBRT + Pembolizumab Experimental Treatment 2 Interventions

Participants receive SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray \[Gy\] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 21 days.

Group II: SBRT + Placebo Placebo Group 2 Interventions

Participants receive SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 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 Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03924869

NCT03924869 | Efficacy and Safety Study of Stereotactic ... The purpose of this study is to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) plus pembrolizumab (MK-3475) in the treatment of adult ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31294749/

Results of the PEMBRO-RT Phase 2 Randomized Clinical ... High-dose radiotherapy can lead to increased tumor antigen release, improved antigen presentation, and T-cell infiltration. This radiotherapy may enhance the ...

3. onclive.com onclive.com/view/pembrolizumab-plus-sbrt-fails-to-improve-survival-in-unresected-stage-i-ii-nsclc

Pembrolizumab Plus SBRT Fails to Improve Survival in ... Pembrolizumab addition to SBRT showed no significant EFS or OS improvement in unresected stage I/II NSCLC compared to placebo. The trial was ...

4. nature.com nature.com/articles/s43018-025-01018-w

Combination of pembrolizumab and radiotherapy induces ... Combination of pembrolizumab and radiotherapy induces systemic antitumor immune responses in immunologically cold non-small cell lung cancer.

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2738064

Effect of Pembrolizumab After Stereotactic Body ... Positive results were largely influenced by the PD-L1–negative subgroup, which had significantly improved progression-free survival and overall ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6624814/

Effect of Pembrolizumab After Stereotactic Body Radiotherapy ... This phase 2 randomized clinical trial assesses whether pembrolizumab after stereotactic body radiotherapy vs pembrolizumab alone enhances tumor response

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.9099

Final results of a phase I prospective trial evaluating the ... Background: We report final Phase I results of a Phase I/II prospective trial assessing safety and tolerability of SBRT and concurrent ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7747230/

Lung Stereotactic Body Radiation Therapy and Concurrent ... Overall, concurrent lung SBRT + ICI is safe. Given the clinically meaningful risk of pneumonitis, closer monitoring should be considered for SBRT + ICI ...