Platform Research for Innovative Medicines in NF2-SWN (PRIME-NF2)

NCT07713745 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: HX-A-2026016
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 5

Brief Summary

This is an adaptive platform-basket trial that aims to evaluate the safety and efficacy of multiple novel agents and combination therapies in patients with NF2-related schwannomatosis (NF2-SWN). The study employs a basket design to assess treatment responses across four tumor types commonly associated with NF2-SWN: vestibular schwannomas, non-vestibular schwannomas, meningiomas, and ependymomas. A shared natural history observational cohort, receiving routine clinical follow-up without investigational treatment, serves as a common control for all substudies. The adaptive platform enables the dynamic addition or closure of substudies based on interim analyses, thereby optimizing trial efficiency. Eligible patients who meet the master protocol criteria and satisfy substudy-specific safety requirements will be assigned to receive the corresponding intervention. Currently open substudies include:

• Substudy A: Selumetinib
• Substudy B: Luvometinib plus Serplulimab

Conditions

Neurofibromatosis Type 2; Vestibular Schwannoma; Non-vestibular Schwannoma; Meningioma; Ependymoma; NF2-related Schwannomatosis; NF2

Outcome Measures

Primary Outcomes (1)

• Tumor-Type-Specific Response Rate in NF2-SWN Tumors

  Vestibular schwannoma: HRR is defined as WRS improvement exceeding the 95% critical difference from baseline; if baseline WRS is \<20%, HRR is defined as a PTA decrease of at least 10 dB. Meningioma or non-vestibular schwannoma: ORR is defined as at least a 20% reduction in target tumor volume from baseline. Ependymoma: ORR is defined as at least a 30% reduction in maximum diameter from baseline according to RECIST v1.1.

  12 months

Secondary Outcomes (6)

• Incidence of Adverse Events in Interventional Substudies

  From first dose through 30 days after last dose (or as specified by individual substudy protocols)

• Maximum Severity Grade of Adverse Events in Interventional Substudies

  12 months

• Incidence of Serious Adverse Events in Interventional Substudies

  From first dose through 30 days after last dose.

• Incidence of Dose Modifications Due to Adverse Events

  From first dose through 30 days after last dose.

• Incidence of Treatment Interruptions Due to Adverse Events

  From first dose through 30 days after last dose.

Other Outcomes (1)

• Change From Baseline in MRI-Based Total Tumor Burden (TTB)

  12 months

Study Arms (3)

Substudy A (Selumetinib)

EXPERIMENTAL

Subjects will receive selumetinib 25 mg/m² by mouth twice daily (single dose not to exceed 50 mg) for up to 12 cycles (28 days per cycle).

Drug: Selumetinib 25mg/m2

Substudy B (Luvometinib + Serplulimab)

EXPERIMENTAL

Subjects will receive luvometinib 8 mg by mouth once daily in combination with serplulimab 4.5 mg/kg intravenously every 3 weeks for up to 12 cycles (28 days per cycle).

Drug: Luvometinib; Drug: Serplulimab

Natural History Cohort

NO INTERVENTION

Participants who are not eligible for any active treatment substudy, or who choose not to receive investigational therapy, will remain in the Natural History Observation Arm. No study intervention will be administered. Participants will undergo standardized longitudinal clinical, imaging, and outcome assessments according to the master protocol. Data collected from this arm will be used to characterize the natural history of NF2-related schwannomatosis and will serve as a shared observational comparator for active treatment arms within the platform.

Interventions

Luvometinib DRUG

Oral once daily per predetermined dosage per protocol.

Also known as: FCN-159

Substudy B (Luvometinib + Serplulimab)

Serplulimab DRUG

Intravenous infusion per predetermined dosage per protocol.

Also known as: HLX10

Substudy B (Luvometinib + Serplulimab)

Selumetinib 25mg/m2 DRUG

Oral twice daily per predetermined dosage per protocol.

Also known as: Koselugo, AZD6244

Substudy A (Selumetinib)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy all of the following criteria to be enrolled into the main study natural history observation cohort:
• (1) Must meet the 2022 International Consensus Criteria for NF2-SWN, defined by having at least one of the following:
• Bilateral vestibular schwannomas (VS)
• An identical NF2 pathogenic variant in at least 2 anatomically distinct NF2-related tumors (schwannoma, meningioma, and/or ependymoma). (Note: if the variant allele fraction (VAF) in unaffected tissues such as blood is clearly \<50%, the diagnosis is mosaic NF2-related schwannomatosis)
• Either 2 major or 1 major and 2 minor criteria as described in the following:
• Major criteria:
• Unilateral VS
• First-degree relative other than sibling with NF2-related schwannomatosis
• or more meningiomas (Note: single meningioma qualifies as minor criteria).
• NF2 pathogenic variant in an unaffected tissue such as blood (Note: if the VAF is clearly \<50%, the diagnosis is mosaic NF2-related schwannomatosis)
• Minor criteria:
• Can count \>1 of a type (eg, 2 distinct schwannomas would count as 2 minor criteria)
• Ependymoma, meningioma (Note: multiple meningiomas qualify as a major criteria), schwannoma (Note: if the major criterion is unilateral VS, at least 1 schwannoma must be dermal in location) Can count only once (eg, bilateral cortical cataracts count as a single minor criterion)
• Juvenile subcapsular or cortical cataract, retinal hamartoma, epiretinal membrane in a person aged \<40 years, meningioma

You may not qualify if:

• Subjects meeting any of the following criteria will not be permitted to enter the main study:
• Coexisting other genetic syndromes that may cause multiple intracranial tumors (e.g., SMARCB1/LZTR1-related schwannomatosis, Cowden syndrome);
• Expected survival \<12 months;
• Presence of severe psychiatric disorders or cognitive impairment that precludes cooperation with imaging or hearing assessments;
• Extreme social or geographic factors that, in the investigator's judgment, may impede follow-up for more than 12 months;

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (5)

Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, 100053, China

Location

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

Location

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

Location

MeSH Terms

Conditions

Neurofibromatosis 2; Neuroma, Acoustic; Meningioma; Ependymoma

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nervous System Neoplasms; Neoplasms by Site; Peripheral Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2026
• First Posted: July 20, 2026
• Study Start: July 18, 2026
• Primary Completion (Estimated): June 1, 2036
• Study Completion (Estimated): December 31, 2036
• Last Updated: July 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)