MK-7684A + Chemotherapy for Lung Cancer

Not currently recruiting at 183 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

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

Disqualifiers: Active malignancy, 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

Compensation: Varies

Number of Visits: 3

Duration: Up to 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new drug combination, pembrolizumab/vibostolimab with chemotherapy, can extend the lives of people with non-small cell lung cancer (NSCLC) more effectively than the current standard treatment. Researchers compare this new combination to the usual treatment of pembrolizumab with chemotherapy. It targets individuals with stage IV NSCLC who have not yet received treatment for their metastatic cancer. Participants must have a confirmed diagnosis of NSCLC and no prior treatment for their metastatic cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or certain immunosuppressive treatments, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that combining pembrolizumab with vibostolimab has a promising safety record for treating non-small cell lung cancer (NSCLC). In earlier studies, patients generally tolerated this combination well. Some experienced side effects, but these were usually manageable.

Pembrolizumab, whether used alone or with other drugs, is already approved for several types of cancer, indicating general safety despite potential side effects like tiredness or nausea. Studies have found that adding vibostolimab to pembrolizumab is well-tolerated.

While ongoing research continues, current evidence suggests that the treatments in this trial are generally safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they could offer new hope for lung cancer patients. The combination of pembrolizumab with vibostolimab is particularly promising, as vibostolimab is a new type of immune checkpoint inhibitor that targets TIGIT, a protein that helps cancer cells evade the immune system. By combining this with pembrolizumab, which targets PD-1, the treatment aims to unleash a more powerful immune response against cancer cells. Unlike standard treatments like chemotherapy alone, this combination could enhance the body's natural ability to fight cancer more effectively. This innovative approach might lead to better outcomes and potentially fewer side effects for patients compared to traditional chemotherapy regimens.

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

Research shows that adding vibostolimab to pembrolizumab may help fight non-small cell lung cancer (NSCLC). Vibostolimab blocks a specific receptor, activating the body's T-cells to attack cancer. Early studies suggest that this combination could strengthen the immune system's response to tumors. In this trial, one group of participants will receive pembrolizumab and vibostolimab with chemotherapy to see if it can improve survival in patients with advanced NSCLC. Another group will receive pembrolizumab alone, already effective in treating various cancers, including NSCLC, and known for helping patients live longer. The combination of pembrolizumab and vibostolimab aims to enhance this effect. Researchers are testing these approaches to determine the most effective treatment strategy. ^{3 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?

This trial is for adults with Stage IV non-small cell lung cancer (NSCLC) who haven't had treatment for metastatic NSCLC, can expect to live at least 3 months, and have measurable disease. They must use effective contraception if of childbearing potential and not have HIV, Hepatitis B/C, other active cancers, CNS metastases, severe allergies to study drugs or their ingredients, certain lung conditions or infections requiring systemic therapy.

Inclusion Criteria

My lung cancer is confirmed to be stage IV.

I haven't had systemic treatment for my advanced lung cancer.

Has measurable disease based on RECIST 1.1, as determined by the local site assessment

Exclusion Criteria

I cannot stop taking aspirin or NSAIDs for 5 days, except for low-dose aspirin.

I have or had lung inflammation that needed steroids.

I am not on high-dose steroids or other drugs that weaken my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab/vibostolimab coformulation or pembrolizumab with chemotherapy for up to 35 cycles (approximately 2 years)

Up to 104 weeks

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 26 months

Open-label extension (optional)

Participants may continue receiving treatment if they benefit and cannot access standard of care outside the study

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Nab-paclitaxel
• Paclitaxel
• Pembrolizumab
• Pembrolizumab/Vibostolimab
• Pemetrexed

Trial Overview The trial tests whether a combination of Pembrolizumab/Vibostolimab with chemotherapy improves overall survival compared to just Pembrolizumab plus chemotherapy in first-time treatment patients with metastatic NSCLC. It's checking the effectiveness of MK-7684A coformulation against established treatments.

How Is the Trial Designed?

Group I: MK-7684A + Chemotherapy Experimental Treatment 6 Interventions

Participants receive pembrolizumab/vibostolimab (co-formulation of 200mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for Squamous NSCLC; PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for Non-squamous.

Group II: Pembrolizumab + Chemotherapy Active Control 6 Interventions

Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for Squamous NSCLC; PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for Non-squamous.

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 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 II trial involving 32 elderly patients with untreated advanced non-small cell lung cancer, the combination of weekly nanoparticle albumin-bound-paclitaxel and carboplatin showed a 50% overall response rate and a median overall survival of 17.5 months, indicating significant efficacy.

The treatment was well tolerated, with no treatment-related deaths or febrile neutropenia reported, and it resulted in less neuropathic toxicity compared to traditional regimens, making it a promising option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Modified Carboplatin Plus Weekly Nab-Paclitaxel in Elderly Patients with Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1301. Miyauchi, E., Inoue, A., Usui, K., et al.[2018]

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]

In a phase II study involving 167 patients with stage IV squamous non-small-cell lung cancer, the combination of necitumumab with paclitaxel-carboplatin chemotherapy resulted in a higher objective response rate (48.9%) compared to chemotherapy alone (40.0%).

The safety profile of necitumumab was consistent with other EGFR monoclonal antibodies, with increased rates of hypomagnesemia and rash, but overall adverse events were low, indicating that necitumumab can be safely combined with chemotherapy for improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer. Spigel, DR., Luft, A., Depenbrock, H., 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]

In a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

In a phase III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., et al.[2022]

In a study involving 812 patients with malignant pleural mesothelioma (MPM), single-agent pemetrexed showed promising efficacy, with a median time to progressive disease of 6.0 months for chemonaïve patients and an overall response rate of 10.5%.

The treatment was well-tolerated, exhibiting mild hematologic toxicity, primarily neutropenia, in less than 18% of patients, indicating a favorable safety profile for pemetrexed in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. Taylor, P., Castagneto, B., Dark, G., et al.[2015]

Citations

1. 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 ...

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

The KEYVIBE program: vibostolimab and pembrolizumab ... The addition of vibostolimab to pembrolizumab has shown promising antitumor activity in non–small-cell lung cancer (NSCLC) in an early clinical ...

3. 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 ...

4. 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 ... Vibostolimab restores antitumor activity by blocking the TIGIT receptor from binding to its ligands (CD112 and CD155), thereby activating T lymphocytes that ...

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

randomized, phase 3 KEYVIBE-008 The KEYVIBE-008 study evaluated vibostolimab coformulated with pembrolizumab (vibostolimab/pembrolizumab) plus EP as first-line therapy for ES-SCLC.

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 ...

7. merck.com merck.com/news/merck-provides-update-on-keyvibe-and-keyform-clinical-development-programs-evaluating-investigational-vibostolimab-and-favezelimab-fixed-dose-combinations-with-pembrolizumab/

Merck Provides Update on KeyVibe and KEYFORM ... In these studies, the safety profile of vibostolimab/pembrolizumab ... lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

8. lungcancerstoday.com lungcancerstoday.com/post/phase-3-keyvibe-008-trial-of-vibostolimab-plus-pembrolizumab-in-es-sclc-discontinued

Phase 3 KeyVibe-008 Trial of Vibostolimab Plus ... The phase 3 KeyVibe-008 trial has been discontinued based on the recommendations of an independent data monitoring committee.