Selumetinib + APG-115 for Neurofibromatosis

(MEKMDM2 Trial)

Not yet recruiting at 1 trial location

Overseen By Rachel E Reed, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AeRang Kim

Must not be taking: Immunosuppressants, Herbal supplements

Disqualifiers: Other cancer, Major surgery, Hypertension, 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 combination of two drugs, Selumetinib (a cancer treatment) and APG-115 (also known as Alrizomadlin, an experimental treatment), to determine their effectiveness in treating individuals with Neurofibromatosis Type 1 who have specific nerve tumors. The goal is to assess whether these drugs can shrink tumors or halt their growth. The trial seeks participants with tumors that cannot be surgically removed or have metastasized. Eligible participants should have previously undergone other cancer treatments and must not have had recent major surgeries or severe medical conditions. As a Phase 1, Phase 2 trial, it aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any other anti-cancer therapies and certain herbal supplements or medications that affect specific liver enzymes at least 14 days before starting the study. If you are on immunosuppressive medications, you must stop them 14 days prior to the study, with some exceptions for low-dose or specific types of steroids.

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

Research has shown that Selumetinib helps treat children with neurofibromatosis type 1, particularly those with inoperable tumors. In a related study, 66% of these cases responded well to the treatment, indicating that Selumetinib is generally safe for these children. Its approval for use in this condition further supports its safety.

For APG-115, less information is available about its safety. It remains under investigation in trials, with researchers closely examining its safety profile. As the trial is in early stages (Phase 1/2), the focus is on understanding its safety and tolerability.

The combination of Selumetinib and APG-115 is being tested to determine their combined efficacy. While Selumetinib has shown positive results independently, the safety of using both treatments together is still under study. Participants in this trial will contribute to understanding the safety and tolerability of this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Selumetinib and APG-115 for treating neurofibromatosis because it offers a novel approach to tackling the condition. Unlike traditional treatments like surgery or radiation, Selumetinib works by inhibiting the MEK enzyme, which plays a key role in the growth of neurofibromas. APG-115 adds another dimension by targeting the MDM2-p53 pathway, which can enhance the body's ability to fight tumor cells. This dual-action approach could provide more effective control over tumor growth and improve outcomes for patients with neurofibromatosis.

What evidence suggests that this treatment might be an effective treatment for Neurofibromatosis?

Research shows that Selumetinib may help treat neurofibromatosis type 1, particularly in children with plexiform neurofibromas that cannot be surgically removed. Studies have found that 66% of these tumors either shrank or stopped growing. Adults taking Selumetinib also reported reduced pain from their tumors. APG-115 blocks a protein that aids cancer cell survival. This trial will study the combination of Selumetinib and APG-115, as they might complement each other by targeting different aspects of tumor growth. Although data on their combined use is limited, the success of each drug individually is promising. ^{1 2 3 4 6}

Who Is on the Research Team?

AeRang Kim, MD, PhD

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

This trial is for patients with Neurofibromatosis Type 1 (NF1) and those who have benign or malignant tumors on their peripheral nerves. Participants should meet specific health criteria not detailed here.

Inclusion Criteria

Fertile men and women of childbearing potential must agree to use an effective method of birth control

My cancer has worsened after chemotherapy, and surgery is planned.

My blood, liver, kidney, and heart are functioning within normal ranges.

Exclusion Criteria

I have eye conditions.

Currently pregnant or breastfeeding

I have had cancer before, but it fits the exceptions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Determine the safety, tolerability, pharmacokinetics, and recommended doses of selumetinib and APG-115

15 months

Treatment Part B

Determine the clinical benefit of selumetinib and APG-115 by evaluating tumor response by imaging

28 months

Treatment Part C

Evaluate the percent apoptosis and tumor proliferation in resected tumor tissue after exposure to selumetinib and APG-115

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• APG-115
• Selumetinib

Trial Overview The study tests the combination of two drugs, Selumetinib (a MEK inhibitor) and APG-115 (an MDM2 inhibitor), to see how they work together in treating NF1-related nerve tumors.

How Is the Trial Designed?

Group I: APG-115 and Selumetinib Experimental Treatment 2 Interventions

There is only one arm. It is combination therapy of APG-115 and Selumetinib.

Who Is Running the Clinical Trial?

AeRang Kim

Lead Sponsor

Trials

3

Recruited

50+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

Published Research Related to This Trial

Selumetinib (KOSELUGO) was approved by the FDA for treating pediatric patients aged 2 and older with inoperable plexiform neurofibromas, showing a 66% overall response rate in a trial of 50 patients, with many experiencing significant symptom relief for at least 12 months.

While selumetinib is effective, it carries risks typical of MEK inhibitors, including potential ocular, cardiac, and gastrointestinal side effects, but the overall benefit-risk assessment is considered favorable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Selumetinib for Plexiform Neurofibroma. Casey, D., Demko, S., Sinha, A., et al.[2022]

Selumetinib, a MEK inhibitor, has shown significant efficacy in treating plexiform neurofibromas in patients with neurofibromatosis type 1, with 68% of 50 symptomatic patients experiencing a partial response and a median tumor volume reduction of 27.9%.

The treatment demonstrated a favorable safety profile, with manageable adverse effects, and resulted in an 84% estimated progression-free survival at 3 years, marking it as the first FDA-approved therapy for inoperable plexiform neurofibromas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Selumetinib in the Treatment of Neurofibromatosis Type 1-Related Plexiform Neurofibromas. Anderson, MK., Johnson, M., Thornburg, L., et al.[2022]

In a clinical trial, the MEK inhibitor selumetinib showed promising results, inducing partial responses in 70% of children with neurofibromatosis type 1 and inoperable plexiform neurofibromas.

The treatment demonstrated a high progression-free survival rate of 84% after 3 years, indicating its potential efficacy in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selumetinib Shrinks Tumors in Neurofibromatosis. [2021]

A Phase I study involving 24 healthy male volunteers evaluated a new granule formulation of selumetinib, showing that its absorption is comparable to the existing capsule form, making it a potential alternative for younger patients or those who have difficulty swallowing capsules.

The study found that the granule formulation was well-tolerated with low incidence of mild adverse events, and participants rated its palatability positively, indicating they would be willing to take it again.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I, Open-label, Randomized, Crossover Study of the Relative Bioavailability of Capsule and Granule Formulations of Selumetinib. Cohen-Rabbie, S., Mattinson, A., So, K., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06735820

NCT06735820 | Early Phase Study Evaluating MEK and ... This is a phase 0/1/2, multi-site study to evaluate the MEK inhibitor Selumetinib with the MDM2 Inhibitor APG-115 in patients with Neurofibromatosis Type 1

2. withpower.com withpower.com/trial/selumetinib-apg-115-for-neurofibromatosis-36806

Selumetinib + APG-115 for Neurofibromatosis Selumetinib has been shown to be effective in treating children with neurofibromatosis type 1 who have inoperable plexiform neurofibromas, with a 66% response ...

3. childrensnational.org childrensnational.org/get-care/departments/neurofibromatosis-institute/clinical-trials

Clinical Trials ACNS1831: A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients with Neurofibromatosis and Low-Grade Glioma · Age: ≥2 years and ≤ 21 years ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39762421/

Selumetinib in adults with NF1 and inoperable plexiform ... Participants experienced decreased tumor pain intensity and pain interference. Adverse events (AEs) were similar to those of the pediatric trial ...

5. synapse.patsnap.com synapse.patsnap.com/drug/4c3cc3cbc2394e6281dd35c803371dd2

Selumetinib sulfate - Drug Targets, Indications, Patents Selumetinib is a MEK inhibitor indicated for pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibromas (PNs).

6. esmorarecancers.org esmorarecancers.org/article/S3050-4619(25)00014-0/fulltext

Mirdametinib approval for neurofibromatosis type 1 with ... With high medication adherence, pooled safety showed a favorable benefit–risk balance in both clinical response and patient-reported outcomes, ...