What side effects are associated with this type of intervention?

Common side effects of treatments for advanced solid tumors, including those similar to KRAS G12C inhibitors like MK-1084, often include gastrointestinal issues (nausea, diarrhea), hematologic toxicities (neutropenia, thrombocytopenia), fatigue, neuropathy, and increased risk of infections. Combination therapies may also lead to more severe side effects such as febrile neutropenia, hypertension, and renal insufficiency. While these side effects can be significant, they are generally manageable with supportive care and dose adjustments.

What prior FDA approvals exist?

The FDA has approved several treatments for solid tumors, including KRAS G12C inhibitors. One notable approval is sotorasib (Lumakras), which targets the KRAS G12C mutation in non-small cell lung cancer (NSCLC). This approval marked a significant advancement in precision oncology, offering a targeted therapy option for patients with this specific genetic mutation. Other treatments for solid tumors often involve a combination of chemotherapy, immunotherapy, and targeted therapies, such as pembrolizumab (Keytruda) and nivolumab (Opdivo), which are used across various cancer types.

What other types of research exist?

Promising alternatives to MK-1084 for KRAS G12C mutant solid tumors include: 1) Sotorasib (AMG 510), another KRAS G12C inhibitor with demonstrated efficacy in clinical trials. 2) Adagrasib (MRTX849), which has shown positive results in targeting KRAS G12C mutations. 3) Combination therapies involving KRAS G12C inhibitors with other agents such as MEK inhibitors or immune checkpoint inhibitors (e.g., pembrolizumab) to enhance treatment efficacy. 4) Investigational drugs targeting other pathways involved in tumor growth and survival, such as SHP2 inhibitors or SOS1 inhibitors, which may provide synergistic effects when used with KRAS G12C inhibitors.

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Small Molecule Inhibitor

MK-1084 + Pembrolizumab for Solid Cancers

Phase 1

Recruiting

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Arm 2 participants must have untreated metastatic non-small cell lung cancer (NSCLC) with histological or blood-based confirmation of KRAS G12C mutation and histologic confirmation of programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%

Arm 6 participants must have untreated locally advanced unresectable or metastatic colorectal adenocarcinoma with histological or blood-based confirmation of KRAS G12C mutation

Must not have

Participants must not have an active infection requiring systemic therapy

Participants must not have specific infectious diseases or conditions

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at designated timepoints during the study in cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. cycle=3 weeks (arms 1-4) and 4 weeks (arms 5-6)

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions at the infusion site, fatigue, digestive issues like nausea and diarrhea from chemotherapy drugs (oxaliplatin/5-fluorouracil), nerve damage from oxaliplatin leading to numbness or tingling in hands/feet. Pembrolizumab may cause immune-related adverse effects such as skin rash or inflammation of organs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My NSCLC is untreated, has a KRAS G12C mutation, and PD-L1 score of 1% or more.

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My colorectal cancer is advanced, cannot be surgically removed, and has a specific KRAS G12C mutation.

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My cancer can be measured and my organs work well.

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My advanced lung cancer has a KRAS G12C mutation and hasn't been treated yet.

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My cancer is advanced, can't be surgically removed, has a KRAS G12C mutation, and I've had at least one treatment.

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My colorectal cancer is advanced, can't be surgically removed, has a KRAS G12C mutation, and I have a specific treatment history.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have an infection that needs treatment with drugs.

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I do not have any infectious diseases.

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I do not have any specific eye conditions.

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I do not have active brain metastases or cancer in the lining of my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at designated timepoints during the study in cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. cycle=3 weeks (arms 1-4) and 4 weeks (arms 5-6)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at designated timepoints during the study in cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. cycle=3 weeks (arms 1-4) and 4 weeks (arms 5-6)

This trial's timeline: 3 weeks for screening, Varies for treatment, and at designated timepoints during the study in cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. cycle=3 weeks (arms 1-4) and 4 weeks (arms 5-6) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants Who Discontinue Study Treatment Due to an AE

Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)

Number of Participants Who Experience an Adverse Event (AE)

Secondary study objectives

Area Under the Concentration Time-Curve 0-12 Hours (AUC 0-12) of MK-1084

Area Under the Concentration Time-Curve 0-24 Hours (AUC 0-24) of MK-1084

Duration of Response (DOR)

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

cetuximab

2000

Completed Phase 3

~7290

leucovorin

2005

Completed Phase 3

~1200

oxaliplatin

2002

Completed Phase 3

~6370

5-fluorouracil

2005

Completed Phase 4

~8440

carboplatin

2010

Completed Phase 3

~4790

Pembrolizumab

2017

Completed Phase 3

~3150

MK-1084

2024

Completed Phase 1

~90

pemetrexed

2005

Completed Phase 3

~5000

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for solid tumors include targeted therapies, immunotherapies, and traditional chemotherapies. Targeted therapies, such as KRAS G12C inhibitors like MK-1084, work by specifically targeting and inhibiting the function of mutated proteins that drive cancer growth, thereby halting tumor progression. Immunotherapies boost the body's immune system to recognize and destroy cancer cells, while traditional chemotherapies kill rapidly dividing cells, including cancer cells, but can also affect normal cells. For patients with solid tumors, these treatments are crucial as they offer more personalized and potentially more effective options, especially for those with specific genetic mutations like KRAS G12C.