Early Phase Study Evaluating MEK and MDM2 Inhibition in Patients With NF1 and MPNST

NCT06735820 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00001200W81XWH-22-1-1120
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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 and pre-malignant and malignant peripheral nerve sheath tumors

Conditions

Malignant Peripheral Nerve Sheath Tumor (MPNST); Neurofibromatosis 1 (NF1); Atypical Neurofibroma

Keywords

NF1; MPNST; MEK inhibitor; MDM2 inhibitor; atypical neurofibroma; ANNUBP

Outcome Measures

Primary Outcomes (2)

• The number of treated patients with adverse events as determined by the common criteria for adverse version 5 (CTCAEv5).

  We will be looking at safety and dose recommendations using adverse event evaluation per dose level as determined by CTCAEv5 (Part A)

  15 months

• Tumor response by imaging using RECISTv1.1

  We will determine the clinical benefit of this combination by evaluating tumor response by imaging using RECISTv1.1 guidelines (Part B)

  28 months

Secondary Outcomes (1)

• Percent apoptosis and tumor proliferation

  12 months

Study Arms (1)

APG-115 and Selumetinib

EXPERIMENTAL

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

Drug: APG-115; Drug: Selumetinib

Interventions

APG-115 DRUG

Combination therapy of APG-115 and Selumetinib

Also known as: alrizomadlin

APG-115 and Selumetinib

Selumetinib DRUG

Combination therapy of APG-115 and Selumetinib

Also known as: koselugo

APG-115 and Selumetinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AGE: Part A and C: ≥ 18 years of age AGE: Part B: ≥12 years (minimum BSA ≥0.55m2)
• Part A and B: Patients with unresectable or metastatic histologically confirmed NF1 associated MPNST. Part C: Patients with NF1 and ANNUBP. Diagnostic criteria based on Miettinen et al, Human Pathol:
• MEASURABLE DISEASE: Patients must have measurable disease by RECISTv1.1. Baseline radiologic scans must be performed within 4 weeks of starting treatment.
• Therapeutic options: Parts A and B: Patients must have experienced progression after one or more prior regimens of cytotoxic chemotherapy. Patients who have refused cytotoxic chemotherapy or for whom treatment on this protocol prior to receiving cytotoxic chemotherapy is felt to be in the best interest for the patient by the local investigator will also be eligible. Part C: Patients with ANNUBP that are planned for surgical resection
• PRIOR THERAPY
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering on this study excluding chronic grade 1 toxicities and alopecia.
• No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study entry.
• Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks (≥21 days) prior to study entry (42 days if prior nitrosourea).
• Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 4 weeks prior to study entry.
• Anti-cancer agents not known to be myelosuppressive (e.g not associated with reduced platelets or ANC count): ≥7 days after the last dose of the agent .
• Radiation therapy: The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks prior to study entry.
• Stem Cell Transplantation. At least 2 months post-autologous stem cell transplant or at least 3 months post-allogeneic transplant and recovered from toxicities without evidence of graft versus host disease and on stable doses of immunosuppressive medications, if required.
• Growth Factors. The last dose of colony stimulating factors, such as filgrastim, sargramostim, and erythropoietin, must be at least 1 week prior to study entry, the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 2 weeks prior to study entry.
• Concurrent therapies: No other anti-cancer therapy (chemotherapy, biological therapy, radiation therapy) permitted.
• PERFORMANCE STATUS

You may not qualify if:

• History of another primary malignancy except for:
• A malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of the study intervention and of low potential risk of recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Stable optic pathway glioma or low-grade glioma not receiving active therapy
• History of leptomeningeal carcinomatosis
• Patients receiving other anti-cancer agents are not eligible.
• Patients who cannot swallow whole pills.
• Current or prior use of immunosuppressive medications within 14 days prior to study entry. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids or local steroid injection (e.g., intra-articular injection)
• Systemic corticosteroids used at physiologic doses not to exceed 10mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Any recent major surgery within a minimum of 4 weeks prior to starting drug therapy. Placement of vascular access device, percutaneous tumor biopsy, or bone marrows are not considered major surgical procedures and no minimum time frame prior to starting study drug therapy is required.
• Patients who have any known severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value corrected for hemoglobin and alveolar volume and/or O2 saturation that is 88% or less at rest on room air. For patients who do NOT have respiratory symptoms (e.g., dyspnea at rest, known requirement for supplemental oxygen), pulmonary function test is not required.

Sponsors & Collaborators

• AeRang Kim: lead
• Children's National Research Institute: collaborator

Study Sites (1)

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

Neurofibrosarcoma; Neurofibromatosis 1

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Neurofibromatoses; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• AeRang Kim, MD, PhD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel E Reed, MS

CONTACT

202-476-3745; rreed@childrensnational.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Pediatric Oncologist

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 16, 2024
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: July 3, 2025

Record last verified: 2025-07

Locations

US (1)