OKI-179 + Binimetinib for Melanoma

No longer recruiting at 13 trial locations

Overseen By Onkure, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: OnKure, Inc.

Must not be taking: Corticosteroids, Valproic acid

Disqualifiers: Pregnancy, Brain metastasis, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with certain types of melanoma, a serious skin cancer, or other tumors with specific genetic mutations. Researchers are combining two drugs, OKI-179 and binimetinib (also known as Mektovi), to determine if they work better together against cancer cells. Patients with melanoma featuring an NRAS mutation or other solid tumors that haven't responded to standard treatments might be suitable candidates, especially if traditional therapies have failed or aren't an option. Participants should have a confirmed NRAS mutation and have tried or be ineligible for certain immune therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not clearly specify if you need to stop taking your current medications. However, you cannot take medications that significantly prolong the QT interval or are strong inhibitors or inducers of certain enzymes and proteins. It's best to discuss your current medications with the trial team.

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

Research shows that combining OKI-179 and binimetinib is generally safe. Earlier studies found that OKI-179 had low rates of serious side effects, suggesting it can be safely combined with other treatments. Binimetinib, already used for certain skin cancers, has proven its safety. Together, these treatments aim to target specific genetic changes in cancer, and early results suggest they work effectively without causing many serious health problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about OKI-179 combined with binimetinib for melanoma because it offers a new approach to tackling the disease. Unlike the standard treatments, which often include immunotherapies and targeted therapies like BRAF inhibitors, OKI-179 is a novel drug that works by inhibiting histone deacetylase (HDAC), a mechanism not commonly targeted in current melanoma treatments. This unique action could potentially disrupt cancer cell growth differently and more effectively. Additionally, pairing OKI-179 with binimetinib, a MEK inhibitor, might enhance treatment effectiveness by simultaneously attacking cancer cells from multiple fronts, providing a promising new strategy for patients with melanoma.

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

Research has shown that combining OKI-179 and binimetinib, the treatment under study in this trial, may help treat NRAS-mutated melanoma, a type of skin cancer. In earlier studies, a similar treatment combination allowed patients to live for about 6.7 months without cancer progression, suggesting that the treatment might slow cancer growth. OKI-179 blocks certain proteins that aid cancer cell growth, while binimetinib targets a specific process in the body that cancer uses to develop. Together, these treatments aim to effectively manage the condition. ^{1 2 3 5 6}

Who Is on the Research Team?

Ryan Sullivan, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

My bilirubin levels are normal or slightly higher due to Gilbert's syndrome.

Exclusion Criteria

I have a muscle disorder that causes high CPK levels.

My high blood pressure is not controlled by medication.

I am not pregnant or nursing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1b

Participants with activating mutations in the RAS pathway receive a combination of oral OKI-179 and binimetinib

1.5 years

Regular visits for monitoring and assessment

Treatment Phase 2

Participants with NRAS-mutated Melanoma receive a combination of oral OKI-179 and binimetinib

3 years

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Binimetinib
• OKI-179

Trial Overview

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.

How Is the Trial Designed?

Group I: OKI-179 + binimetinib Experimental Treatment 1 Intervention

Binimetinib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in European Union as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Approved in Canada as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in Japan as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

OnKure, Inc.

Lead Sponsor

Trials

3

Recruited

220+

Citations

1.

onclive.com

onclive.com/view/bocodepsin-binimetinib-is-tolerable-shows-combinatorial-activity-in-nras-mutant-metastatic-melanoma

Bocodepsin/Binimetinib Is Tolerable, Shows ... - OncLive

The combination of bocodepsin and binimetinib showed a median progression-free survival of 6.7 months in NRAS-mutant metastatic melanoma ...

2.

onkuretherapeutics.com

onkuretherapeutics.com/onkure-therapeutics-announces-first-patient-dosed-in-the-phase-1b-2-nautilus-trial-of-oki-179-in-combination-with-binimetinib-in-patients-with-advanced-nras-mutated-melanoma/

OnKure Therapeutics Announces First Patient Dosed in ...

The Phase 1b/2 Nautilus study is an open-label, dose-escalation and expansion trial designed to determine the safety and efficacy of OKI-179 ...

3.

onkuretherapeutics.com

onkuretherapeutics.com/onkure-and-pfizer-enter-clinical-trial-collaboration-and-supply-agreement-to-evaluate-combination-of-oki-179-and-binimetinib/

OnKure and Pfizer Enter Clinical Trial Collaboration and ...

MEKTOVI (binimetinib) in combination with OKI-179, a highly potent and tolerable Class I HDAC inhibitor currently in Phase I for the treatment of NRAS melanoma.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05340621

NCT05340621 | NAUTILUS: OKI-179 Plus Binimetinib in ...

OKI-179 will be administered on a 4-days-on/3-days-off schedule, while binimetinib will be administered BID continuously. Phase 2: Patients will be treated with ...

5.

withpower.com

withpower.com/trial/phase-2-melanoma-3-2022-0f827

OKI-179 + Binimetinib for Melanoma · Info for Participants

This trial tests a combination of two oral medications, OKI-179 and binimetinib, in patients with specific genetic mutations in their cancer.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10778198/

First-in-Human Dose-Escalation Study of the Novel Oral ...

OKI-179 was well tolerated with low rates of high-grade adverse events, supporting the potential for the successful combination of OKI-179 with ...