~491 spots leftby Feb 2030

MK-1084 + Pembrolizumab for Solid Cancers

Recruiting at68 trial locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Merck Sharp & Dohme Corp.
Must not be taking: NSAIDs, Steroids, others
Disqualifiers: CNS metastases, Active infection, Autoimmune, others
No Placebo Group
Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called MK-1084, alone or with other treatments, in patients with advanced cancers that have a specific mutation. The drug aims to block this mutation to stop or slow down the cancer. Another drug, Sotorasib, was the first approved treatment for this type of cancer.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are in Arm 4, you must be able to interrupt aspirin or other NSAIDs for a few days around the administration of pemetrexed.

What data supports the effectiveness of the drug pembrolizumab in treating solid cancers?

Pembrolizumab has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and melanoma, by improving survival rates and showing high response rates with minimal side effects.12345

Is the combination of MK-1084 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, and nausea. Serious side effects, such as pneumonitis (lung inflammation), occur in a small percentage of patients. Always discuss potential risks with your healthcare provider.12367

What makes the drug MK-1084 + Pembrolizumab unique for treating solid cancers?

The combination of MK-1084 and Pembrolizumab is unique because it involves using Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells, alongside MK-1084, which may have a different mechanism of action. This combination could potentially enhance the effectiveness of the immune response against solid tumors compared to using Pembrolizumab alone.12356

Research Team

MD

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced solid tumors that have a specific mutation (KRAS G12C). Participants must have measurable disease, proper organ function, and agree to contraception. It's not suitable for pregnant or breastfeeding women, those with active infections like HIV or hepatitis, certain eye conditions, recent vaccines, autoimmune diseases requiring treatment, CNS metastases/carcinomatous meningitis, or who can't take required supplements.

Inclusion Criteria

My NSCLC is untreated, has a KRAS G12C mutation, and PD-L1 score of 1% or more.
My colorectal cancer is advanced, cannot be surgically removed, and has a specific KRAS G12C mutation.
My cancer can be measured and my organs work well.
See 6 more

Exclusion Criteria

I meet the specific medication requirements for Arm 4.
I am willing to take specific medications for the trial.
I do not have an infection that needs treatment with drugs.
See 6 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-1084 alone or in combination with other therapies, with cycles varying between 3 and 4 weeks depending on the arm, for up to 24 months

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 56 months

Treatment Details

Interventions

  • MK-1084 (Small Molecule Inhibitor)
  • Pembrolizumab (Checkpoint Inhibitor)
Trial OverviewThe study tests MK-1084 alone and combined with Pembrolizumab in patients with KRAS G12C mutant tumors. It aims to assess the effectiveness and safety of these treatments in different groups: some untreated NSCLC cases; others who've had systemic therapy; and various stages of colorectal cancer after previous therapies failed.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: Arm 6Experimental Treatment5 Interventions
Participants will receive MK-1084 daily oral dose. Additionally, participants receive an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle, oxaliplatin (per label) for first 6 cycles, and leucovorin (per label) and 5-fluorouracil (per label) once every 14-days.
Group II: Arm 5Experimental Treatment2 Interventions
Participants will receive MK-1084 daily oral dose plus an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle.
Group III: Arm 4Experimental Treatment4 Interventions
Participants will receive MK-1084 daily oral dose plus an intravenous infusion of pembrolizumab (200 mg) once every 21-day cycle for up to 35 cycles (up to \~24 months). Participants will also receive carboplatin (per label) and pemetrexed (per label) once every 21-day cycle for the first 4 cycles.
Group IV: Arm 3Experimental Treatment1 Intervention
Participants will receive alternate formulation of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.
Group V: Arm 2Experimental Treatment2 Interventions
Participants will receive MK-1084 daily oral escalating dose of up to 800 mg plus pembrolizumab given as a 200 mg intravenous infusion once every 21-day cycle up to a total of 35 cycles (up to \~24 months). Treatment with MK-1084 will continue until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.
Group VI: Arm 1Experimental Treatment1 Intervention
Participants will receive daily oral escalating doses of up to 800 mg of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials
2,287
Recruited
4,582,000+
Chirfi Guindo profile image

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 profile image

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 profile image

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 profile image

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

Findings from Research

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.
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]
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.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions.Karim, S., Leighl, N.[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.
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]

References

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]
Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]
Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]