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

2026년 7월 14일 업데이트: Beijing Tiantan Hospital

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

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

This is an investigator-initiated, prospective, multicenter, adaptive platform-basket clinical trial designed to evaluate the safety and efficacy of multiple therapies in patients with NF2-related schwannomatosis (NF2-SWN). The study includes four tumor baskets: vestibular schwannoma, meningioma, non-vestibular schwannoma, and ependymoma.

MASTER STUDY All patients with a confirmed diagnosis of NF2-SWN who provide written informed consent will be enrolled in the master study and enter the natural history observational cohort. Patients who meet eligibility criteria for one or more active substudies may be assigned to a corresponding treatment arm. When multiple treatment arms are open, allocation will follow a predefined randomization scheme. When only one treatment arm is available, eligible patients may be enrolled directly into that substudy. Patients not eligible for any active intervention will remain in the master study cohort for standardized follow-up.

Patients who experience progression of the target tumor during substudy treatment may be considered for enrollment into another active treatment arm if eligibility criteria are met. Patients who are not eligible for any active substudy will return to the master study observational cohort. Data collected during follow-up may serve as shared control data across the platform.

Patients in the observational cohort will undergo standardized follow-up assessments every 12 months until study completion or voluntary withdrawal. Patients receiving treatment within a substudy will undergo efficacy and safety assessments approximately every 3 months according to the corresponding substudy protocol. The master study plans to enroll at least 200 patients with NF2-SWN, with enrollment continuing over time as eligible patients are identified across participating centers.

SUBSTUDY 1: Selumetinib

  • Selumetinib is a selective MEK1/2 inhibitor approved for the treatment of NF1-associated plexiform neurofibromas. It inhibits tumor growth through blockade of the RAS/RAF/MEK/ERK signaling pathway.
  • This substudy plans to enroll 20 patients, prioritizing those with vestibular schwannoma as the target tumor. Detailed eligibility criteria are provided in the substudy protocol.

SUBSTUDY 2: Luvometinib + Serplulimab

  • Luvometinib is a selective oral MEK1/2 inhibitor. Serplulimab is a humanized anti-PD-1 monoclonal antibody that blocks PD-1 signaling and restores T-cell-mediated antitumor immune activity by preventing interaction with PD-L1 and PD-L2.
  • This substudy plans to enroll approximately 30 adult patients, prioritizing those with vestibular schwannoma or meningioma as the target tumor. Detailed inclusion and exclusion criteria are described in the substudy protocol.

Each substudy protocol will be incorporated into the master protocol as an appendix. Addition of new substudies requires review and approval by the Data and Safety Monitoring Board (DSMB).

Efficacy will be evaluated using tumor-specific endpoints. For vestibular schwannoma, the primary endpoint is Hearing Response Rate (HRR). For meningioma, non-vestibular schwannoma, and ependymoma, the primary endpoint is radiographic Objective Response Rate (ORR). All efficacy endpoints will undergo blinded central review by an Independent Review Committee (IRC).

The platform is expected to remain active for 5-10 years, or until all active substudies are completed and no additional treatment arms are planned.

연구 유형

중재적

등록 (추정된)

200

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 중국
    • Beijing Municipality
      • Beijing, Beijing Municipality, 중국, 100853
        • Chinese PLA General Hospital
        • 연락하다:
      • Beijing, Beijing Municipality, 중국, 100070
        • Beijing Tiantan Hospital, Capital Medical University
        • 연락하다:
      • Beijing, Beijing Municipality, 중국, 100053
        • Xuanwu Hospital, Capital Medical University
        • 연락하다:
    • Jilin
      • Changchun, Jilin, 중국, 130021
        • The First Hospital of Jilin University
        • 연락하다:
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, 중국, 200080
        • Shanghai General Hospital
        • 연락하다:

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 어린이
  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

Eligibility Specific For MASTER STUDY

Inclusion Criteria:

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:

  1. Bilateral vestibular schwannomas (VS)
  2. 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)
  3. 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
  • 2 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

    (2) Presence of at least one evaluable lesion: Vestibular schwannoma, meningioma, or non-vestibular schwannoma: clearly identifiable lesion on contrast-enhanced T1-weighted MRI; Ependymoma: clearly identifiable lesion on contrast-enhanced T1-weighted or T2/FLAIR sequences; (3) Expected ability to complete at least 12 months of follow-up assessments; (4) Ability to understand and voluntarily sign a written informed consent form, or a legally authorized guardian signs the informed consent form together ; (5) Sub-study-specific criteria (for intervention arms only): If the subject intends to enter an interventional sub-study, in addition to meeting the above main study criteria, the subject must also satisfy the specific inclusion criteria specified in that sub-study protocol (e.g., organ function, prior treatment restrictions, washout periods, etc.), as determined by the drug characteristics.

Exclusion Criteria:

Subjects meeting any of the following criteria will not be permitted to enter the main study:

  1. Coexisting other genetic syndromes that may cause multiple intracranial tumors (e.g., SMARCB1/LZTR1-related schwannomatosis, Cowden syndrome);
  2. Expected survival <12 months;
  3. Presence of severe psychiatric disorders or cognitive impairment that precludes cooperation with imaging or hearing assessments;
  4. Extreme social or geographic factors that, in the investigator's judgment, may impede follow-up for more than 12 months;
  5. Sub-study-specific exclusion criteria (for intervention arms only): If the subject intends to enter an interventional sub-study, the subject must also satisfy the specific exclusion criteria specified in that sub-study protocol (e.g., specific organ dysfunction, active infection, pregnancy, etc.).

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Substudy A (Selumetinib)
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).
의약품: Selumetinib 25mg/m2
Oral twice daily per predetermined dosage per protocol.
다른 이름들:
  • 코셀루고
  • AZD6244
실험적: Substudy B (Luvometinib + Serplulimab)
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).
의약품: Luvometinib
Oral once daily per predetermined dosage per protocol.
다른 이름들:
  • FCN-159
의약품: Serplulimab
Intravenous infusion per predetermined dosage per protocol.
다른 이름들:
  • HLX10
간섭 없음: Natural History Cohort
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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Tumor-Type-Specific Response Rate in NF2-SWN Tumors
기간: 12 months

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

2차 결과 측정

결과 측정
측정값 설명
기간
Incidence of Adverse Events in Interventional Substudies
기간: From first dose through 30 days after last dose (or as specified by individual substudy protocols)
Percentage of participants receiving active treatment who experience at least one adverse event. Adverse events will be coded and graded according to NCI CTCAE v5.0.
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
기간: 12 months
Maximum NCI CTCAE v5.0 grade of adverse events experienced by each participant during the reporting period.
12 months
Incidence of Serious Adverse Events in Interventional Substudies
기간: From first dose through 30 days after last dose.
Percentage of participants receiving active treatment who experience at least one serious adverse event.
From first dose through 30 days after last dose.
Incidence of Dose Modifications Due to Adverse Events
기간: From first dose through 30 days after last dose.
Percentage of participants receiving active treatment who require at least one dose modification due to an adverse event.
From first dose through 30 days after last dose.
Incidence of Treatment Interruptions Due to Adverse Events
기간: From first dose through 30 days after last dose.
Percentage of participants receiving active treatment who require at least one treatment interruption due to an adverse event.
From first dose through 30 days after last dose.
Incidence of Treatment Discontinuations Due to Adverse Events
기간: From first dose through 30 days after last dose.
Percentage of participants receiving active treatment who discontinue treatment due to an adverse event.
From first dose through 30 days after last dose.

기타 결과 측정

결과 측정
측정값 설명
기간
Change From Baseline in MRI-Based Total Tumor Burden (TTB)
기간: 12 months
TTB will be assessed using serial MRI. TTB is calculated as the sum of the volumes of all prespecified measurable NF2-SWN-related tumors included in the tumor-burden assessment. The outcome is the relative percentage change in TTB from baseline to 12 months, based on blinded central radiology review.
12 months

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Beijing Tiantan Hospital

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 7월 18일

기본 완료 (추정된)

2036년 6월 1일

연구 완료 (추정된)

2036년 12월 31일

연구 등록 날짜

최초 제출

2026년 7월 3일

QC 기준을 충족하는 최초 제출

2026년 7월 14일

처음 게시됨 (실제)

2026년 7월 20일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 7월 20일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 7월 14일

마지막으로 확인됨

2026년 5월 1일

추가 정보

이 연구와 관련된 용어

추가 관련 MeSH 약관

기타 연구 ID 번호

  • HX-A-2026016

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

미국에서 제조되어 미국에서 수출되는 제품

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

뇌실막종에 대한 임상 시험

Luvometinib에 대한 임상 시험

유사한 임상시험 검색

스폰서 및 공동 작업자

건강 상태

약물 개입

CROs by country

CROs in Turkmenistan

정황

희귀 질병

약물 개입

식이 보충제

스폰서 / 협력자

위치

3
구독하다