Luvometinib in Combination With Serplulimab for NF2-Related Tumors

A Multicenter, Open-Label Study of Luvometinib in Combination With Serplulimab for the Treatment of NF2-Related Tumors

This is an investigator-initiated, exploratory, multicenter, open-label, single-arm clinical trial and a substudy of the Platform Research for Innovative Medicines in NF2-SWN (PRIME-NF2). The study aims to evaluate the safety, tolerability, and preliminary efficacy of luvometinib in combination with serplulimab in patients with NF2-related schwannomatosis (NF2-SWN) with progressive tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Meningioma; Neurofibromatosis Type 2; Vestibular Schwannoma; NF2; NF2-related Schwannomatosis
• Intervention / Treatment: Drug: Luvometinib; Drug: Serplulimab

Detailed Description

NF2-related schwannomatosis (NF2-SWN) is a rare autosomal dominant disorder characterized by multiple central nervous system tumors, most commonly vestibular schwannomas and meningiomas. Although current treatments such as surgery and radiotherapy can provide disease control, they are not curative and are associated with cumulative neurological morbidity and potential risk of secondary malignancies. There remains a significant unmet need for effective systemic therapies.

This investigator-initiated study is conducted as a substudy within the Platform Research for Innovative Medicines in NF2-SWN (PRIME-NF2). The trial evaluates luvometinib in combination with serplulimab in patients with progressive NF2-SWN.

Luvometinib (FCN-159) is a selective MEK1/2 inhibitor with antitumor activity in NF1-associated tumors. Serplulimab (HLX10) is an anti-PD-1 monoclonal antibody approved for multiple solid tumors. Preclinical evidence suggests that MEK inhibition may enhance tumor immunogenicity and synergize with immune checkpoint blockade.

The study aims to assess the safety, tolerability, and preliminary efficacy of this combination in NF2-SWN.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Chinese PLA General Hospital
      • Contact: Jun Zhang, MD, PhD; Phone Number: 86+ 10-68182255; Email: junzhang301@163.com
    • Beijing, Beijing Municipality, China, 100070
      • Beijing Tiantan Hospital, Capital Medical University
      • Contact: Pinan Liu, MD, PhD; Phone Number: 86+ 10-59976611; Email: pinanliu@ccmu.edu.cn
    • Beijing, Beijing Municipality, China, 100053
      • Xuanwu Hospital, Capital Medical University
      • Contact: Hao Wu, MD, PhD; Phone Number: +86 10-83922345; Email: wuhaospine@xwh.ccmu.edu.cn
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
      • Contact: Yunqian Li, MD, PhD; Phone Number: 86+ 431-88782222; Email: yunqian@jlu.edu.cn
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200080
      • Shanghai General Hospital
      • Contact: Meiqing Lou, MD, PhD; Phone Number: +86 21-63846590; Email: loumq68128@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must meet the diagnostic criteria for NF2-SWN.
2. Presence of at least one measurable target tumor, either vestibular schwannoma or meningioma, with MRI-documented volumetric progression within the past 36 months or clinical symptom progression related to the target tumor.
3. The target tumor is considered unsuitable for surgery because of high risk.
4. Age >=18 years at the time of screening.
5. KPS >=70 or ECOG performance status 0 or 1.
6. Adequate organ function based on laboratory tests obtained within 14 days before screening.
7. Participant must be able to understand the study and voluntarily sign informed consent.

Exclusion Criteria:

1. Pregnant, planning to become pregnant, or currently breastfeeding.
2. Participation in another interventional clinical trial within the past 4 weeks, or radiation therapy to target lesion(s) within the past 3 years.
3. Severe adverse reactions or intolerable toxicity from prior immune checkpoint inhibitors or MEK inhibitors.
4. Concomitant active malignancies, uncontrolled infections, or active autoimmune diseases.
5. Severe cardiac, hepatic, renal, gastrointestinal, or ophthalmic diseases.
6. Any other factor that may compromise participant safety or study integrity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Luvometinib; Oral once daily per predetermined dosage per protocol.; Other Names: FCN-159; Drug: Serplulimab; Intravenous infusion per predetermined dosage per protocol.; Other Names: HLX10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) or Hearing Response Rate (HRR)	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: ORR is defined as at least a 20% reduction in target tumor volume from baseline.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events	Percentage of participants 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 (up to 12 months)
Maximum Severity Grade of Adverse Events	Maximum NCI CTCAE v5.0 grade of adverse events experienced by each participant during the reporting period.	From first dose through 30 days after last dose (up to 12 months)
Incidence of Serious Adverse Events	Percentage of participants who experience at least one serious adverse event.	From first dose through 30 days after last dose (up to 12 months)
Incidence of Dose Modifications	Percentage of participants who require at least one dose modification due to an adverse event.	From first dose through 30 days after last dose (up to 12 months)
Incidence of Treatment Interruptions	Percentage of participants 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	Percentage of participants who discontinue study treatment due to an adverse event.	From first dose through 30 days after last dose.

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: July 3, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Genetic Diseases, Inborn; Neoplasms by Histologic Type; Neurodegenerative Diseases; Otorhinolaryngologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neuroendocrine Tumors; Ear Diseases; Otorhinolaryngologic Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Cranial Nerve Diseases; Neuroma; Cranial Nerve Neoplasms; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Neurofibroma; Neurilemmoma; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurofibromatoses; Meningioma; Neuroma, Acoustic; Neurofibromatosis 2
• Other Study ID Numbers: HX-A-2026035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No