Mirdametinib + BGB-3245 for Advanced Cancer

No longer recruiting at 13 trial locations

Overseen By SpringWorks Clinical

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: SpringWorks Therapeutics, Inc.

Must not be taking: CYP3A4 inhibitors, inducers

Disqualifiers: CNS metastases, Cardiac disease, 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 two drugs, mirdametinib and BGB-3245 (also known as Brimarafenib), to determine their effectiveness in treating advanced cancers that no longer respond to other treatments. It targets individuals with specific genetic changes in their cancer, such as mutations in the MAPK pathway, NRAS, KRAS, or BRAF genes. Participants should have advanced cancer that has either spread or cannot be surgically removed and must have tried at least one other treatment that was ineffective or poorly tolerated. Those with solid cancer that has progressed despite treatment and contains one of these genetic changes may qualify for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering a chance to contribute to groundbreaking cancer treatment advancements.

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

The trial requires that you stop taking any systemic anti-cancer therapy and certain other medications, like glucocorticoids and strong CYP3A4 inhibitors or inducers, at least 2 weeks before starting the trial. If you're on these medications, you may need to stop them before participating.

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

Research shows that BGB-3245 may help treat solid tumors and generally has a manageable safety profile. While some side effects might occur, they are usually not serious. In earlier studies, patients tolerated the treatment well, indicating its safety in humans.

The FDA has already approved Mirdametinib for treating certain tumors in both adults and children, meaning it has passed strict safety tests for that use. However, its safety in combination with BGB-3245 is still under investigation.

These findings suggest that the combination of BGB-3245 and Mirdametinib is expected to be well-tolerated. However, like any trial, there may be risks, and participants should discuss these with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Mirdametinib and BGB-3245 because they offer a fresh approach to tackling advanced cancers, particularly those with mutations in the MAPK pathway. Unlike traditional treatments that may not specifically target these mutations, Mirdametinib is a MEK inhibitor, while BGB-3245 is a RAF dimer inhibitor, both of which directly interfere with the cancer cell signaling pathways that drive tumor growth. This targeted action could potentially lead to more effective treatments for cancers like cutaneous melanoma and non-small cell lung cancer (NSCLC) with specific genetic mutations. By honing in on these pathways, these drugs could offer new hope for patients who haven't responded well to existing therapies.

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

Research has shown that BGB-3245, one of the treatments in this trial, produces promising results in treating solid tumors. In early trials, it shrank or slowed tumor growth. Mirdametinib, another treatment option, blocks a protein called MEK1, which helps stop cancer cells from growing. Studies have shown that mirdametinib led to tumor shrinkage in 42% of patients. Together, these treatments target cancer cell pathways to reduce tumor size and slow cancer progression. These results suggest that the combination could be effective for certain advanced cancers, especially those with specific genetic mutations. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that haven't improved with at least one prior treatment, or when no other treatments are available. Participants must be over 18, have a performance status of ≤2 (which means they can do some light activity), and have specific genetic changes in their tumor related to the MAPK pathway. They should not have had recent cancer therapy or surgery, and cannot join if they have certain medical conditions like severe heart disease or uncontrolled infections.

Inclusion Criteria

Measurable disease per RECIST 1.1

Able to provide informed consent

My organs are functioning well and I haven't had a transfusion in the last 14 days.

Exclusion Criteria

I have a parathyroid disorder or had cancer-related high calcium levels.

I cannot swallow pills.

I haven't had cancer treatment in the last 2 weeks or 5 half-lives.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of mirdametinib and BGB-3245 to determine the maximum tolerated dose

Up to 18 months

Dose Expansion

Participants receive the recommended phase 2 dose of mirdametinib and BGB-3245 to evaluate efficacy and safety

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• BGB-3245
• Mirdametinib

Trial Overview The trial is testing a combination of two drugs: Mirdametinib and BGB-3245. It's an early-phase study where doses are increased gradually to find safe levels before expanding to more patients. The goal is to see how well these drugs work together against different types of solid tumors with mutations affecting cell growth pathways.

How Is the Trial Designed?

Group I: Phase 2 Dose Expansion C Experimental Treatment 2 Interventions

Participants with NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutation or BRAF Fusion mutation

Group II: Phase 2 Dose Expansion B Experimental Treatment 2 Interventions

Participants with NSCLC harboring KRAS mutations

Group III: Phase 2 Dose Expansion A Experimental Treatment 2 Interventions

Participants with cutaneous melanoma harboring NRAS mutations

Group IV: Phase 1 Dose Escalation Cohorts Ranging in Dose Experimental Treatment 2 Interventions

Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway

Who Is Running the Clinical Trial?

SpringWorks Therapeutics, Inc.

Lead Sponsor

Trials

14

Recruited

900+

Citations

1. targetedonc.com targetedonc.com/view/bgb-3245-demonstrates-efficacy-in-solid-tumors-with-a-mutation-in-the-mapk-pathway

BGB-3245 Demonstrates Efficacy in Solid Tumors With a ... The investigational drug BGB-3245 showed encouraging anti-tumor activity with a manageable safety profile in a first-in-human phase 1a/1b trial.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05580770

Mirdametinib + BGB-3245 in Advanced Solid Tumors A Phase 1/2a open-label, multicenter, dose escalation and expansion study of mirdametinib in combination with BGB-3245 in adult participants.

3. springworkstx.gcs-web.com springworkstx.gcs-web.com/news-releases/news-release-details/mapkure-springworks-and-beigene-present-clinical-data-bgb-3245/

Press Release Details - SpringWorks Therapeutics This ongoing Phase 1a/1b trial (NCT04249843) is an open-label, dose escalation and expansion study of BGB-3245 in adult patients with advanced ...

4. ir.springworkstx.com ir.springworkstx.com/news-releases/news-release-details/beigene-and-springworks-therapeutics-announce-formation-mapkure

Press Release Details BeiGene and SpringWorks Therapeutics announce the formation of MapKure to develop BGB-3245, an investigational, selective next-generation RAF kinase inhibitor.

5. delta.larvol.com delta.larvol.com/Products/?ProductId=f5e053c7-92a6-43a6-9e98-083cac32292d

brimarefenib (BGB-3245) / MapKure, BeOne Medicines, ... ... cancer patients with known MAPK pathway mutations. MapKure expects to initiate a Phase 1b trial in the first quarter of 2024....The FDA cleared the IND ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT04249843

Study of Safety, Pharmacokinetics, and Antitumor Activity ... ... BGB-3245, an investigational, selective RAF dimer inhibitor, in adult patients with advanced or refractory solid tumors harboring MAPK pathway aberrations.