Mirdametinib + Sirolimus for Multiple Myeloma

Overseen By Elizabeth M Hill, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, BCRP inhibitors

Disqualifiers: Plasma cell leukemia, Amyloidosis, Heart failure, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with relapsed or refractory multiple myeloma (RRMM), a type of blood cancer that often returns after treatment or doesn't respond to it. Researchers are testing two drugs, mirdametinib (a MEK inhibitor) and sirolimus (an mTOR inhibitor), which may target cancer cells with specific gene changes in KRAS or NRAS. The trial aims to determine the optimal dose and assess the effectiveness of the combination. It seeks participants with RRMM who have these specific gene changes and have tried several previous treatments without success.

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 treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop other myeloma-directed therapy (except for radiation) at least 14 days before starting the study treatment. Additionally, participants must not take certain medications that strongly interact with specific enzymes (CYP3A4 and BCRP) within 14 days prior to starting the trial.

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

Research is examining the safety of using mirdametinib and sirolimus together for patients with relapsed or refractory multiple myeloma (RRMM). Previous studies have assessed patients' tolerance to this combination, carefully tracking side effects using standard methods to ensure patient safety.

The research is ongoing, so complete safety information is not yet available. As this study is in its early stages, it primarily aims to determine a safe dose and observe patient responses to the treatment. The treatment is still under safety evaluation, and researchers will closely monitor any side effects.

Overall, while earlier research provides some information, this study will offer more details about the safety of these drugs when used together in people with RRMM. Participants will undergo regular monitoring to address any side effects promptly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Mirdametinib and Sirolimus for multiple myeloma because it offers a novel approach to tackling the disease. Unlike standard treatments like proteasome inhibitors and immunomodulatory drugs, this combo targets different pathways involved in cancer cell growth. Mirdametinib inhibits the MEK enzyme, which is part of a signaling pathway that many cancers exploit to proliferate, while Sirolimus suppresses a key protein that cancer cells use for survival. This dual action could potentially lead to more effective control of the disease, offering hope for improved outcomes.

What evidence suggests that mirdametinib and sirolimus could be effective for relapsed refractory multiple myeloma?

This trial will evaluate the combination of mirdametinib and sirolimus for patients with relapsed refractory multiple myeloma (RRMM) who have specific changes in their KRAS or NRAS genes. Studies have shown that using mirdametinib and sirolimus together may target these genetic changes in cancer cells, potentially enhancing treatment effectiveness. Early findings suggest that this combination might help overcome drug resistance, a major challenge in treating multiple myeloma. Although more research is needed, initial results are promising for improving patient outcomes. ^{1 3 4 5 6}

Who Is on the Research Team?

Elizabeth M Hill, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed refractory multiple myeloma (RRMM) who have specific genetic changes (KRAS or NRAS mutations). Participants must provide proof of their disease and mutation status, undergo various screenings including blood tests, imaging scans, an eye exam, heart function test, and a bone marrow biopsy.

Inclusion Criteria

Participants must have measurable disease per International Myeloma Working Group (IMWG) criteria

Participants must agree to use contraception as specified if of childbearing potential or able to father a child

Participants seropositive for HIV, HCV, or HBV must meet specific criteria related to their infection status

Exclusion Criteria

Positive beta-HCG serum or urine pregnancy test performed in IOCBP at screening

I haven't taken certain medications or substances in the last 14 days.

Participant has abnormal QT interval corrected by Fridericia's formula

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Finding (Phase 1b)

Determine the recommended phase 2 dose (RP2D) of mirdametinib in combination with sirolimus using a standard 3 + 3 design

4 weeks

Weekly visits during the first cycle

Treatment (Phase 2)

Evaluate the efficacy of mirdametinib at RP2D in combination with sirolimus for 12 cycles (1 year)

12 months

Weekly visits during the first cycle, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Mirdametinib and Sirolimus

Trial Overview The study is testing the combination of two oral drugs: mirdametinib (capsules) taken twice daily for three weeks in a four-week cycle and sirolimus (tablets) taken once daily throughout the cycle. The first part determines a safe dosage; the second part assesses effectiveness against RRMM.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 2 Interventions

Sirolimus and RP2D of mirdametinib

Group II: Arm 1 Experimental Treatment 2 Interventions

Sirolimus and escalating doses of mirdametinib

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Recent advancements in anti-myeloma treatments, including thalidomide, lenalidomide, and bortezomib, have shown significant clinical responses, especially in patients who do not respond to traditional chemotherapy.

The review highlights the ongoing development of various novel therapeutic classes, such as second-generation proteasome inhibitors and HDAC inhibitors, which are currently in clinical trials or advanced preclinical stages, indicating a promising expansion of treatment options for myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. Mitsiades, CS., Hayden, PJ., Anderson, KC., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06876142

NCT06876142 | Combination Therapy (Mirdametinib and ... Phase 2: To determine the preliminary efficacy of mirdametinib at RP2D in combination with sirolimus in participants with RAS mutated RRMM as assessed by the ...

2. withpower.com withpower.com/trial/mirdametinib-sirolimus-for-multiple-myeloma-8e35f

Mirdametinib + Sirolimus for Multiple Myeloma Additionally, similar combinations have shown the ability to overcome drug resistance and improve patient outcomes in multiple myeloma.

3. themmrf.org themmrf.org/diagnosis-and-treatment/clinical-trials-and-emerging-therapies/clinical-trial-finder/

Clinical Trial Finder Tool This study tests a combination of two oral medications, mirdametinib and sirolimus, in patients with relapsed or treatment-resistant multiple myeloma who have ...

4. sparkcures.com sparkcures.com/clinical-trials/multiple-myeloma

Multiple Myeloma Clinical Trials We help myeloma patients find, understand and connect with their clinical trial options at centers around the US.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666634024001788

Potential utility of cancer drugs in nonmalignant illnesses Targeted compounds used successfully to treat cancer may have therapeutic potential for nonmalignant conditions harboring the same target.

6. clin.larvol.com clin.larvol.com/trial-detail/NCT06876142

Combination Therapy (Mirdametinib and Sirolimus) for ... The number and frequency of adverse events for participants as assessed per CTCAE version 5. Safety will be analyzed by reporting the number of patients ...