Pembrolizumab/Vibostolimab + Chemoradiotherapy for Non-Small Cell Lung Cancer

(KEYVIBE-006 Trial)

Not currently recruiting at 210 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, Immunosuppressants, NSAIDs, others

Disqualifiers: SCLC, Immunodeficiency, 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

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial seeks better treatment options for people with locally advanced non-small cell lung cancer (NSCLC). The study tests whether combining pembrolizumab and vibostolimab with standard chemotherapy and radiotherapy can help patients live longer without cancer progression compared to those receiving durvalumab. People with Stage III NSCLC, who have not received previous treatments and whose cancer cannot be surgically removed, might be suitable candidates. The trial seeks participants with this specific type of lung cancer to explore these new treatment combinations. As a Phase 3 trial, it represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take certain medications like chronic systemic steroids, immunosuppressive therapy, or NSAIDs around the time of pemetrexed administration. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or certain other treatments, you may need to adjust or stop them before starting the trial.

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

Research has shown that the combination of pembrolizumab and vibostolimab has been tested in people with non-small cell lung cancer (NSCLC) and has produced promising results. Studies indicate that this combination exhibits strong anti-cancer effects.

Regarding safety, previous patients have generally tolerated the pembrolizumab/vibostolimab combination well, with most side effects being mild to moderate. However, like any treatment, some serious side effects can occur, so discussing these with a doctor is important.

Since this trial is in a later phase, a substantial amount of safety information is already available. This suggests the treatment is reasonably safe, but ongoing research remains important to learn more. Always consider discussing potential risks with a healthcare professional before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Pembrolizumab/Vibostolimab is unique because it combines two immune checkpoint inhibitors, pembrolizumab and vibostolimab, which may enhance the immune system's ability to target and destroy cancer cells more effectively than standard therapies. Unlike traditional treatments that mainly rely on chemotherapy and radiotherapy, this combination is designed to provide a more robust immune response. Researchers are excited because this dual-acting treatment might improve outcomes for patients with non-small cell lung cancer by offering a more targeted approach. Meanwhile, the durvalumab arm serves as an active comparator and works by blocking the PD-L1 pathway, which helps the body’s immune system recognize and fight cancer cells. Both approaches aim to harness the power of the immune system, potentially offering more durable responses than conventional treatments.

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

Research has shown that the combination of pembrolizumab and vibostolimab, which participants in this trial may receive, holds promise for treating non-small cell lung cancer (NSCLC). In earlier studies, this treatment helped patients live an average of 2.4 months longer without their cancer worsening. These drugs have demonstrated a strong ability to fight cancer cells, offering hope for people with NSCLC seeking new treatment options. ^{1 2 3 5 6}

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 Stage III Non-small Cell Lung Cancer (NSCLC) who haven't had previous treatments. They must have a life expectancy of at least 6 months, be able to provide a tumor tissue sample, and not show signs of cancer spread in scans. Participants should be physically capable (ECOG status 0 or 1) and cannot have an active infection, recent vaccines, other cancer treatments within the last month, autoimmune diseases treated in the past two years, or certain medical conditions.

Inclusion Criteria

My scans show no signs of cancer spread beyond my lungs.

You are expected to live for at least 6 months.

My lung cancer is at Stage III and cannot be removed by surgery.

Exclusion Criteria

I have received drugs to boost my white blood cells within the last 28 days.

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

I have not had major surgery in the last 4 weeks or have fully recovered from it if I did.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Concurrent Chemoradiotherapy

Participants receive concurrent chemoradiotherapy with platinum doublet chemotherapy and standard thoracic radiotherapy

9 weeks

3 cycles of 21-day cycles

Consolidation Therapy

Participants receive durvalumab or pembrolizumab/vibostolimab as consolidation therapy

up to 14 months

Every 2 weeks for durvalumab, every 3 weeks for pembrolizumab/vibostolimab

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 75 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Durvalumab
• Etoposide
• Paclitaxel
• Pembrolizumab/Vibostolimab
• Thoracic Radiotherapy

Trial Overview The study tests pembrolizumab/vibostolimab with chemoradiotherapy (cCRT), followed by more pembrolizumab/vibostolimab against cCRT followed by durvalumab. It aims to see if the first combination is better for extending survival without cancer progression and overall survival in patients whose tumors express PD-L1 protein.

How Is the Trial Designed?

Group I: pembrolizumab/vibostolimab coformulation+chemotherapy+radiotherapy Experimental Treatment 8 Interventions

For the first 3 cycles, participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) intravenously (IV) on Day 1 plus 3 cycles of investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy during Cycles 2, 3. Participants receive pembrolizumab/vibostolimab for Cycles 4-20 or until discontinuation (up to \~14 months). Cycles 1-20 are 21-day cycles. As of protocol amendment 4, participants receiving pembrolizumab/vibostolimab must stop ongoing treatment with pembrolizumab/vibostolimab and will be offered the option to transition to post-cCRT durvalumab consolidation therapy, to complete up to 1 year of consolidation immunotherapy.

Group II: chemotherapy+radiotherapy+durvalumab Active Control 7 Interventions

For the first 3 cycles, participants will receive investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy during Cycles 2 and 3. Following concurrent chemoradiotherapy (cCRT), participants receive durvalumab 10 mg/kg every 2 weeks for up to an additional 26 cycles or until discontinuation (up to approximately 14 months). cCRT Cycles 1-3=21-day cycles; durvalumab Cycles 1-26=14-day cycles.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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

Published Research Related to This Trial

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., 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]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

A case study of a 52-year-old man with HIV and lung adenocarcinoma showed that combining pembrolizumab with stereotactic body radiotherapy led to serious immune-related adverse events, including massive pericardial effusion and interstitial pneumonia.

Despite initial treatment with pembrolizumab and radiotherapy, the patient's condition worsened, highlighting the need for caution and further clinical trials to assess the safety and efficacy of this combination therapy in HIV-infected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report. Li, D., He, C., Xia, Y., et al.[2018]

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]

In the KEYNOTE-407 study involving 1107 patients with untreated metastatic squamous non-small-cell lung cancer, the addition of pembrolizumab to chemotherapy significantly improved overall survival and quality of life without increasing severe toxicity.

Patients receiving pembrolizumab reported better health-related quality of life scores at weeks 9 and 18 compared to those receiving placebo, indicating that pembrolizumab enhances patient well-being while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. Mazieres, J., Kowalski, D., Luft, A., 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]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

In the KEYNOTE-407 study, pembrolizumab combined with chemotherapy significantly improved overall survival (17.1 months) and progression-free survival (8.0 months) compared to placebo plus chemotherapy in patients with untreated metastatic squamous non-small cell lung cancer (NSCLC).

The study also found that patients receiving pembrolizumab plus chemotherapy had a longer time before disease progression on subsequent treatments (PFS-2), supporting its use as a standard first-line therapy, despite a similar rate of serious adverse events (grade 3 to 5) between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. Paz-Ares, L., Vicente, D., Tafreshi, A., et al.[2021]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

Citations

1. merck.com merck.com/news/merck-announces-findings-from-phase-2-keyvibe-002-trial-evaluating-an-investigational-coformulation-of-vibostolimab-and-pembrolizumab-in-previously-treated-patients-with-metastatic-non-small-cell-lung/

Merck Announces Findings from Phase 2 KeyVibe-002 ... Data presented at ESMO I-O showed that vibostolimab/pembrolizumab plus docetaxel extended median progression-free survival (PFS) by 2.4 months compared to those ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11497960/

The KEYVIBE program: vibostolimab and pembrolizumab ... Background & rationale. The addition of vibostolimab to pembrolizumab has shown promising antitumor activity in non–small-cell lung cancer ( ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05226598

NCT05226598 | Study of Pembrolizumab/Vibostolimab ... The primary hypothesis is that pembrolizumab/vibostolimab (MK-7684A) in combination with chemotherapy is superior to pembrolizumab in combination with ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS9160

A randomized, double-blind, phase 3 trial of MK-7684A ... The phase 3 KeyVibe-007 (NCT05226598) study is evaluating the efficacy and safety of pembro and vibostolimab, coformulated as MK-7684A, in combination with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04725188

Study Details | NCT04725188 | Pembrolizumab ... The main purpose of this study is to compare pembrolizumab/vibostolimab coformulation (MK-7684A) plus docetaxel or pembrolizumab/vibostolimab coformulation ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05298423

NCT05298423 | Study of Pembrolizumab/Vibostolimab ... The goal of this study is to learn if people who receive the combination of vibostolimab and pembrolizumab (MK-7684A) live longer without the cancer getting ...