What is the mechanism of action of this treatment?

MEK inhibitors, such as binimetinib, target the MEK enzyme in the MAPK/ERK pathway, which is frequently overactive in melanoma due to mutations in proteins like BRAF or NRAS. By inhibiting MEK, these drugs can decrease cell proliferation and promote apoptosis in melanoma cells. This targeted approach is important for melanoma patients as it offers a more effective and personalized treatment option, potentially improving outcomes and minimizing side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for melanoma, particularly those involving MEK inhibitors like Binimetinib, often have side effects including cutaneous reactions (rash, photosensitivity), gastrointestinal issues (nausea, diarrhea), and ocular effects (blurred vision, retinal vein occlusion). Other side effects can include fever, fatigue, and increased liver enzymes. These treatments aim to inhibit the MEK pathway, which is crucial in melanoma cell proliferation. While the specific side effects of OKI-179 are not well-documented, it is important to monitor for any adverse reactions during treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for melanoma that involve MEK inhibition. Notably, the combination of dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) has been approved for the treatment of BRAF V600E-mutant melanoma. This combination has shown significant efficacy in improving overall response rates and progression-free survival in patients with advanced melanoma. Additionally, other MEK inhibitors like cobimetinib, in combination with vemurafenib (another BRAF inhibitor), have also received FDA approval for similar indications. These treatments target the MAPK/ERK pathway, which is often dysregulated in melanoma.

What other types of research exist?

Promising novel alternatives for melanoma treatment in 2024 include: <ol> <li>Immune Checkpoint Inhibitors: Pembrolizumab and Nivolumab, which target PD-1, and Ipilimumab, which targets CTLA-4.</li> <li>BRAF Inhibitors: Dabrafenib and Vemurafenib, particularly for patients with BRAF V600 mutations.</li> <li>Combination Therapies: Combining BRAF inhibitors with MEK inhibitors like Trametinib or Cobimetinib to enhance efficacy and reduce resistance.</li> <li>LAG-3 Inhibitors: Relatlimab, which targets LAG-3, showing promise in combination with Nivolumab.</li> <li>Oncolytic Virus Therapy: Talimogene laherparepvec (T-VEC), an oncolytic viral therapy that selectively infects and kills cancer cells while stimulating an immune response.</li> </ol>

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OKI-179 + Binimetinib for Melanoma

Phase 1 & 2

Waitlist Available

Led By Ryan Sullivan, MD

Research Sponsored by OnKure, Inc.

Eligibility Criteria Checklist

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

Must have

Phase 2: Prior ICI treatment with a programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) checkpoint inhibitor, or ineligible for this type of therapy

Phase 1b: Solid tumor refractory to standard treatment, for which no standard therapy is available, or if the patient refuses standard therapy

Must not have

Patients who have neuromuscular disorders that are associated with elevated creatine phosphokinase (CPK; eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) or elevated baseline CPK levels (≥ Grade 2)

Known positive serology for HIV and AIDS-related illness with CD4 count < 350/mL and/or known active hepatitis B or hepatitis C. Testing prior to C1D1 is not required

Timeline

Screening 3 weeks

Treatment Varies

Follow Up phase 1b study duration (approximately 1.5 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two oral medications, OKI-179 and binimetinib, in patients with specific genetic mutations in their cancer. It targets those with RAS pathway mutations and NRAS-mutated Melanoma. The treatment works by blocking signals that help cancer cells grow and divide. Binimetinib is a selective MEK1/2 inhibitor approved in 2018 for the treatment of metastatic melanomas with BRAF and NRAS mutations.

Who is the study for?

This trial is for adults with advanced solid tumors in the RAS pathway or NRAS-mutated melanoma. They must have normal organ and marrow function, be able to swallow oral meds, and not be pregnant or nursing. Exclusions include hypersensitivity to MEK inhibitors, certain eye conditions, uncontrolled heart disease, severe infections like HIV/AIDS, recent major surgery or chemotherapy.

What is being tested?

The NAUTILUS study tests OKI-179 combined with binimetinib on patients with specific mutations in their tumors. Phase 1b focuses on various solid tumors while Phase 2 targets NRAS-mutated melanoma specifically. It's an open-label study where everyone knows what treatment they're getting.

What are the potential side effects?

Potential side effects may include typical reactions to cancer medications such as fatigue, digestive issues (nausea/vomiting), skin rash from binimetinib use, liver enzyme changes requiring monitoring of blood tests regularly and possible visual disturbances due to drug sensitivity.

Eligibility Criteria

Inclusion Criteria

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

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I have previously been treated with or am ineligible for PD-1/PD-L1 therapy.

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My solid tumor hasn't responded to standard treatments, or there are none available, or I refuse them.

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My melanoma is metastatic with a confirmed NRAS mutation.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I can take pills by mouth without difficulty.

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My tumor has a mutation in the RAS pathway.

Exclusion Criteria

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

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I have a muscle disorder that causes high CPK levels.

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I have HIV/AIDS with a CD4 count below 350, or active hepatitis B or C.

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My high blood pressure is not controlled by medication.

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I am not pregnant or nursing.

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I am currently taking medication that strongly affects liver enzyme levels.

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I do not have conditions that would make taking pills difficult.

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I have not used specific cancer treatments like HDAC inhibitors or MEK inhibitors.

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I have not had major surgery in the last 4 weeks.

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I am currently taking medication that strongly affects drug transport in my body.

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I have a history of long QT syndrome.

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I have not had chemotherapy or radiation in the last 2 weeks.

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I do not have serious heart problems.

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I have a history of specific eye conditions or risks for them, like uncontrolled glaucoma.

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I am on medication that affects my heart's rhythm.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ phase 1b study duration (approximately 1.5 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~phase 1b study duration (approximately 1.5 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and phase 1b study duration (approximately 1.5 years) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Phase 1b: Change in clinical laboratory abnormalities

Phase 1b: Incidence and severity of adverse events (AEs)

Phase 1b: Incidence and severity of dose-limiting toxicities (DLTs)

+1 more

Secondary study objectives

Phase 1b: Area Under the Plasma Concentration vs. Time Curve (AUC) of OKI-179 and OKI-006

Phase 1b: Clinical Benefit Rate (CBR)

Phase 1b: Duration of Response (DOR)

+8 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: OKI-179 + binimetinibExperimental Treatment1 Intervention

0 / 20Eligibility 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

MEK inhibitors, such as binimetinib, target the MEK enzyme in the MAPK/ERK pathway, which is frequently overactive in melanoma due to mutations in proteins like BRAF or NRAS. By inhibiting MEK, these drugs can decrease cell proliferation and promote apoptosis in melanoma cells. This targeted approach is important for melanoma patients as it offers a more effective and personalized treatment option, potentially improving outcomes and minimizing side effects compared to traditional chemotherapy.