MK-1084 + Pembrolizumab for Solid Cancers

(KANDLELIT-001 Trial)

Recruiting at 86 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: NSAIDs, Steroids, others

Disqualifiers: CNS metastases, Active infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

830 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug, MK-1084, both alone and with other treatments like pembrolizumab (an immunotherapy drug), for advanced solid tumors with the KRAS G12C mutation. The trial focuses on evaluating the treatments' effectiveness and potential side effects. Individuals with advanced solid tumors, such as lung or colorectal cancer, who have the KRAS G12C mutation and have previously tried at least one other treatment, may be suitable candidates for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

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

Research has shown that MK-1084, whether used alone or with other treatments, has a manageable safety profile. Studies have found that people taking MK-1084, either by itself or with drugs like cetuximab (a cancer treatment), experienced generally mild and manageable side effects.

When combined with pembrolizumab (another cancer treatment), early results suggest MK-1084 remains safe with manageable side effects. This combination has shown promising results in both safety and effectiveness.

In summary, evidence so far suggests that MK-1084, whether used alone or with drugs like pembrolizumab or cetuximab, is generally well-tolerated by patients. While some side effects may occur, they are usually not serious and can be managed with proper care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they bring innovative approaches to tackling solid cancers. Unlike standard chemotherapy, which targets rapidly dividing cells, MK-1084 works by potentially inhibiting specific pathways that cancer cells use to grow. When combined with pembrolizumab, an immune checkpoint inhibitor, this duo could boost the immune system's ability to fight cancer more effectively. Additionally, the combination with cetuximab in some treatment arms offers a targeted therapy approach, which can be more specific in attacking cancer cells while sparing healthy ones. These features could enhance treatment efficacy and reduce side effects compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that MK-1084, a new cancer drug, holds promise for treating certain advanced cancers. In this trial, participants in different arms will receive MK-1084 in various combinations. Early findings suggest that MK-1084, both alone and combined with cetuximab (another cancer treatment), can help shrink tumors. Studies also indicate that using MK-1084 with pembrolizumab, an immune therapy, is generally safe and effective in fighting tumors. Specifically, about 47% of patients in these studies experienced tumor shrinkage with this combination. These results offer hope for people with advanced solid tumors that have a specific genetic mutation. ^{2 4 5 6 7}

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 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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• MK-1084
• Pembrolizumab

Trial Overview The 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.

How Is the Trial Designed?

Group I: Arm 6 Experimental Treatment 5 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 5 Experimental Treatment 2 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 4 Experimental Treatment 4 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 3 Experimental Treatment 1 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 2 Experimental Treatment 2 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 1 Experimental Treatment 1 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.

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 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]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

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 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]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3508

The KRAS G12C inhibitor MK-1084 for ... Here, we report data for MK-1084 monotherapy, MK-1084 + cetuximab, and MK-1084 + cetuximab + mFOLFOX6 in pts with advanced KRAS G12C-mutant CRC.

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. merck.com merck.com/news/merck-announces-mk-1084-an-investigational-kras-g12c-inhibitor-shows-antitumor-activity-in-phase-1-trial-of-patients-with-advanced-colorectal-cancer-and-non-small-cell-lung-cancer-whose-tumors-harbo/

Merck Announces MK-1084, an Investigational KRAS ... Manageable safety profile and encouraging antitumor activity observed for MK-1084 in KANDLELIT-001, both as a monotherapy and in studied ...

4. esmoopen.com esmoopen.com/article/S2059-7029(24)00041-3/pdf

44O Updated results from a phase I study evaluating the ... Conclusions: MK-1084 as monotherapy and in combination with pembro showed manageable safety and preliminary antitumor activity in pts with previously treated.

5. asco.org asco.org/abstracts-presentations/ABSTRACT433620

A phase 1, open-label, multicenter study evaluating MK ... The first MK-1084 clinical study and aims to evaluate it as monotherapy and combination therapy in patients (pts) with advanced solid tumors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07209111

NCT07209111 | A Clinical Study of MK-1084 in People ... Researchers want to learn if MK-1084 given alone or with cetuximab can treat certain advanced solid tumors in people with the KRAS G12C mutation ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02686-8/fulltext

663P Safety and preliminary efficacy of the KRAS G12C ... MK-1084 as monotherapy and in combination with pembro showed manageable safety and preliminary antitumor activity in pts with previously treated solid ...