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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Oral once daily per predetermined dosage per protocol.
Intravenous infusion per predetermined dosage per protocol.
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Chinese PLA General Hospital
Beijing, Beijing Municipality, China
The First Hospital of Jilin University
Changchun, Jilin, China
Shanghai General Hospital
Shanghai, Shanghai Municipality, China
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.
Time frame: 12 months
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From first dose through 30 days after last dose.
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