MK-1084 + Pembrolizumab for Lung Cancer

Recruiting at 244 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Small cell lung cancer, Cardiovascular disease, Autoimmune disease, 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: 1

Duration: Up to approximately 56 months

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of combining MK-1084, an experimental treatment, with pembrolizumab for certain types of advanced lung cancer. It targets individuals with non-small cell lung cancer (NSCLC) who have a KRAS G12C mutation and a high PD-L1 tumor score, specific genetic features of the cancer. The researchers aim to determine if this combination can extend patients' lives and slow cancer progression compared to pembrolizumab alone. Individuals newly diagnosed with advanced NSCLC who meet these genetic criteria might be suitable for this study. 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 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 MK-1084 with pembrolizumab is generally safe for patients with non-small cell lung cancer that has the KRAS G12C mutation. This indicates that side effects are usually manageable. Early studies have also found that this combination may help shrink tumors, suggesting potential effectiveness.

Pembrolizumab already has FDA approval for treating other cancers and possesses a well-established safety record, which boosts confidence in the safety of this treatment. Although this specific combination remains under investigation, current evidence suggests that patients generally tolerate it well. ^{1 2 3 4 5}

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

Researchers are excited about MK-1084 in combination with pembrolizumab for lung cancer because it offers a novel approach compared to standard treatments. Most current therapies focus on inhibiting cancer growth through immune checkpoints or targeting tumor cells directly. However, MK-1084 introduces a unique mechanism by acting on a specific pathway that may enhance the immune response against cancer cells, potentially improving outcomes when paired with pembrolizumab. This combination could provide a new option for patients, with the potential for increased effectiveness over current treatments.

What evidence suggests that the combination of MK-1084 and pembrolizumab could be an effective treatment for non-small cell lung cancer?

This trial will compare two treatment arms for lung cancer. In one arm, participants receive MK-1084 with pembrolizumab. Studies have shown that this combination shows promise in fighting tumors and is generally safe for patients with non-small cell lung cancer (NSCLC) with KRAS G12C mutations. Early evidence suggests this combination might help slow or stop cancer growth in these patients.

In the other arm, participants receive a placebo with pembrolizumab. Pembrolizumab is already known to help the immune system fight cancer cells. When combined with MK-1084, which targets a specific change in cancer cells, the treatment could be more effective. While more research is needed, initial results are hopeful for people with this type of lung cancer. ^{1 3 4 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 a specific mutation in their lung cancer (KRAS G12C) and high levels of a protein called PD-L1. They must have advanced lung cancer that has spread, and they haven't been treated before. People can't join if they've had certain other treatments or health conditions that the study lists.

Inclusion Criteria

Has life expectancy of at least 3 months

I agree to use contraception if I can produce sperm.

My cancer has the KRAS G12C mutation.

Exclusion Criteria

I have had lung inflammation that needed steroids or currently have it.

I do not have uncontrolled heart or brain blood vessel problems.

I have not had radiotherapy in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles and either MK-1084 or placebo by oral tablets once daily

Up to approximately 56 months

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 56 months

What Are the Treatments Tested in This Trial?

Interventions

• MK-1084
• Pembrolizumab

Trial Overview The study tests MK-1084 combined with Pembrolizumab against a placebo plus Pembrolizumab to see which is better at slowing down cancer growth or improving survival rates in patients with this type of advanced lung cancer.

How Is the Trial Designed?

Group I: MK-1084 with Pembrolizumab Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and MK-1084 by oral tablets until discontinuation criterion is met.

Group II: Placebo with Pembrolizumab Active Control 2 Interventions

Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met.

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

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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

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]

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]

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 (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., 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]

Citations

1. merck.com merck.com/news/merck-initiates-phase-3-clinical-trial-of-mk-1084-an-investigational-oral-kras-g12c-inhibitor-in-combination-with-keytruda-pembrolizumab-for-first-line-treatment-of-certain-patients-with-met/

Merck Initiates Phase 3 Clinical Trial of MK-1084, an ... “Based on early evidence showing MK-1084 in combination with KEYTRUDA had a manageable safety profile and promising anti-tumor activity, we are ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05067283

NCT05067283 | A Study of MK-1084 in KRAS Mutant ... This is a study evaluating the safety, pharmacokinetics, and efficacy of MK-1084 alone, and MK-1084 plus other combination therapies in participants with ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02966-1/pdf

1392TiP Phase III study of pembrolizumab plus MK-1084 ... These two tumor types are rare, with limited data on their clinical, anatomopathological, and biological characteristics.Their prognosis is poor, with low rate ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11907553/

Immunotherapy in advanced, KRAS G12C-mutant non- ... The combination of MK-1084 plus pembrolizumab 200 mg IV q3w was administered in patients with untreated, metastatic NSCLC with PD-L1 ⩾1%. Of the ...

5. cancernetwork.com cancernetwork.com/view/pembrolizumab-mk-1084-combo-is-the-focus-of-phase-3-trial-in-kras-g12c-metastatic-nsclc

Pembrolizumab/MK-1084 Combo Is the Focus of Phase 3 ... MK-1084 previously demonstrated manageable safety and preliminary activity in non–small cell lung cancer harboring KRAS G12C mutations as ...

6. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/investigational-mk-1084-demonstrates-antitumor-activity-trial-colorectal-non-small-cell-lung-cancers

Investigational MK-1084 Demonstrates Antitumor Activity ... MK-1084, Merck's investigational KRAS G12C inhibitor, showed a manageable safety profile along with antitumor activity in the Phase I KANDLELIT-001 study.