Coformulated Pembrolizumab/Vibostolimab for Non-Small Cell Lung Cancer

Not currently recruiting at 260 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, Corticosteroids

Disqualifiers: Active infection, Autoimmune disease, CNS metastases, 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: Unknown

Duration: Up to 105 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with metastatic non-small cell lung cancer (NSCLC) that expresses the PD-L1 protein. Researchers aim to determine if combining two drugs, vibostolimab and pembrolizumab (an immunotherapy drug), can extend the time patients live without cancer progression, compared to using pembrolizumab alone. Suitable candidates for this trial have NSCLC that has spread, is PD-L1 positive, and have not received certain previous cancer treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.

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 steroids or immunosuppressive therapy, you may need to stop or adjust them before starting the study.

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

Research has shown that combining vibostolimab and pembrolizumab has been studied for safety in treating non-small cell lung cancer (NSCLC). Patients have generally tolerated the addition of vibostolimab to pembrolizumab well, with no major safety issues reported in these studies. Some side effects were noted, but they were usually manageable.

Pembrolizumab alone is already approved for use in various cancers, indicating a known safety profile. The combination with vibostolimab is being studied to ensure it doesn't significantly alter this safety profile. So far, results are promising, suggesting that the combination might be safe for humans.

Overall, current research suggests this treatment is fairly safe, but discussing options with a doctor is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the coformulated treatment of pembrolizumab and vibostolimab for non-small cell lung cancer because it combines two powerful components in one infusion. While pembrolizumab alone is already a standard treatment option, targeting the PD-1 pathway to help the immune system attack cancer cells, the addition of vibostolimab introduces a new mechanism by also targeting TIGIT, another immune checkpoint. This dual targeting approach potentially enhances the immune response against cancer, offering a more comprehensive attack on the tumor. By combining these mechanisms, the treatment aims to improve effectiveness and provide better outcomes for patients.

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

This trial will compare the effectiveness of Pembrolizumab/Vibostolimab with Pembrolizumab alone for treating non-small cell lung cancer (NSCLC). Studies have shown that combining vibostolimab with pembrolizumab may aid in treating NSCLC. Research suggests this combination can extend the time patients live without their cancer worsening by about 2.4 months compared to standard treatments. Vibostolimab enhances the immune system's ability to recognize and attack cancer cells. Pembrolizumab is already effective in treating several types of cancer, including NSCLC, by blocking a protein that allows cancer to evade the immune system. Together, these treatments show promising results in slowing cancer progression. ^{1 2 3 4 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 IV non-small cell lung cancer (NSCLC) showing PD-L1 expression in at least 1% of tumor cells. Participants must not need EGFR-, ALK-, or ROS1-directed therapy, have a life expectancy of over 3 months, and an ECOG score of 0-1. Women must use effective contraception or be abstinent, and all participants should have adequate organ function.

Inclusion Criteria

My tumor shows PD-L1 expression in at least 1% of cells.

You have a measurable disease according to specific medical guidelines.

My cancer is not suitable for EGFR, ALK, or ROS1 therapy.

Exclusion Criteria

I have a history of Hepatitis B or an active Hepatitis C infection.

I have stable brain metastases and haven't needed steroids for 14 days.

I have no health issues that prevent me from receiving standard lung cancer chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either pembrolizumab/vibostolimab as a coformulation or pembrolizumab monotherapy

Up to 105 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 68 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Pembrolizumab/Vibostolimab

Trial Overview The study tests if a combination drug (pembrolizumab/vibostolimab) is more effective than pembrolizumab alone in improving survival without cancer progression. It focuses on patients whose tumors express the protein PD-L1 to varying degrees and measures overall survival and disease progression.

How Is the Trial Designed?

Group I: Pembrolizumab/Vibostolimab Experimental Treatment 1 Intervention

Participants received 200 mg pembrolizumab / 200 mg vibostolimab as a coformulation (MK-7684A) by intravenous (IV) infusion every 3 weeks (Q3W) for up to 35 administrations, until centrally verified disease progression, or until a protocol specified discontinuation criterion was met. Per investigator's discretion, eligible participants with stable disease, or partial/complete response who received a first course treatment may have received a second course of treatment based on original randomization assignment for up to 17 cycles (up to \~1 year).

Group II: Pembrolizumab Active Control 1 Intervention

Participants received 200 mg pembrolizumab by IV infusion Q3W for up to 35 administrations, until centrally verified disease progression, or until a protocol-specified discontinuation criterion was met. Per investigator's discretion, eligible participants with stable disease, or partial/complete response who received a first course treatment may have received second course of treatment based on original randomization assignment for up to 17 cycles (up to \~1 year).

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

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., 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]

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 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]

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]

An elderly male patient on pembrolizumab developed four autoimmune toxicities, including type 1 diabetes and pneumonitis, highlighting the risk of multiple immune-related adverse events associated with this treatment.

The case suggests that aging may increase susceptibility to these adverse effects, necessitating close monitoring and prompt management, including stopping the immunotherapy and using steroids for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. Kethireddy, N., Thomas, S., Bindal, P., et al.[2021]

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 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, 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]

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. jitc.bmj.com jitc.bmj.com/content/12/Suppl_3/A1693

randomized, phase 3 KEYVIBE-008 First-line pembrolizumab plus EP significantly improved PFS but not OS vs placebo plus EP in ES-SCLC in the KEYNOTE-604 study.2 Vibostolimab, an ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04738487

Study Details | NCT04738487 | Coformulation of ... The goal of this study is to learn if people who receive vibostolimab and pembrolizumab live longer overall and without the cancer getting worse.