HLX-1502 for Neurofibromatosis (INSPIRE-NF1 Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Healx Limited
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The trial will be an open label, single arm, phase 2 study in 20 participants. The study will assess the tolerability and efficacy of HLX-1502 in participants with NF1 16 years of age or older with progressive and/or symptomatic PN.
What makes the drug HLX-1502 unique for treating neurofibromatosis?
HLX-1502 is a novel treatment for neurofibromatosis type 2, a condition with no FDA-approved systemic therapies that address its underlying biology. Unlike traditional management, which primarily involves surgery and symptom treatment, HLX-1502 may target the molecular pathways involved in the disease, potentially offering a new approach to managing the condition.
12345Will I have to stop taking my current medications?
The trial requires that participants stop taking certain medications before enrolling, including MEK-inhibitors, other drugs in the TKI class, myelosuppressive chemotherapy, and other systemic anti-cancer treatments. If you are on any of these medications, you will need to stop them before joining the trial.
Eligibility Criteria
This trial is for individuals at least 16 years old with Neurofibromatosis Type 1 (NF1) who have progressive or symptomatic plexiform neurofibromas (PNs). Participants need measurable PNs suitable for MRI analysis, good performance status, and proper organ function. They must not be planning other treatments for the lesion during the study and agree to use effective contraception if applicable.Inclusion Criteria
I weigh at least 49 kg.
I can do most of my daily activities by myself.
My bone marrow, kidneys, liver, and pancreas are working well, and my blood pressure is under control.
I am not planning any surgery or treatments for my cancer lesion other than those specified in the study.
I have been diagnosed with NF1 according to the 2021 criteria.
My tumors are growing or causing significant health issues.
Participant Groups
The trial tests HLX-1502's safety and effectiveness in patients with NF1. It's an open-label, single-arm Phase 2 study involving 20 participants who will receive this experimental treatment to see how well it works on their tumors.
1Treatment groups
Experimental Treatment
Group I: HLX-1502Experimental Treatment1 Intervention
Participants will take an oral dose three times a day (with or without food) for 12 cycles. A cycle is defined as 28 days. Participants with a partial response or stable disease with a previously progressive tumor and/or clinical improvement can continue therapy for an additional 12 cycles for a total of 24 cycles.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of Alabama at BirminghamBirmingham, AL
Children's Hospital of PhiladelphiaPhiladelphia, PA
Indiana UniversityIndianapolis, IN
Cincinnati Children's Hospital Medical CenterCincinnati, OH
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Who is running the clinical trial?
Healx LimitedLead Sponsor
References
[Neurofibromatosis type 2 (central neurofibromatosis or bilateral acoustic neuromas, vestibular schwannomas): from phenotype to gene]. [2009]Neurofibromatosis type 2 (NF2) is an autosomal dominant disease that predisposes to bilateral vestibular schwannomas (neurinomas), other central and peripheral nervous system tumours (multiple meningeomas and neurofibromas) and ocular abnormalities (cataract). The NF2 tumour suppresor gene is localised on chromosome 22q12 and encodes protein called schwannomin or merlin which is related to a family of cytoskeleton-to-membrane proteins linkers ERM (ezrin-radixin-moesin proteins). About 50% of all cases are new germline mutations, although about 20% of apparently sporadic cases represent somatic mosaicism. The majority of observed germline NF2 mutations are point mutations which result in schwannomin with an altered or absent C-terminal domain. NF2 has a variable clinical presentation, with two basic types: severe type having early onset and progressive growth of tumors and the milder type having later onset and less aggressive course. The genotype-phenotype correlations indicate a greater variability of clinical disease expression. In this paper we discuss the epidemiology, genetic and clinical characteristics, diagnostic criteria, investigations, screening for risk persons and recommendations for care and therapy of patients with NF2.
Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. [2019]Neurofibromatosis type 2 [NF2; MIM # 101000] is an autosomal dominant disorder characterised by the occurrence of vestibular schwannomas (VSs), schwannomas of other cranial, spinal and cutaneous nerves, cranial and spinal meningiomas and/or other central nervous system (CNS) tumours (e.g., ependymomas, astrocytomas). Additional features include early onset cataracts, optic nerve sheath meningiomas, retinal hamartomas, dermal schwannomas (i.e., NF2-plaques), and (few) café-au-lait spots. Clinically, NF2 children fall into two main groups: (1) congenital NF2 - with bilateral VSs detected as early as the first days to months of life, which can be stable/asymptomatic for one-two decades and suddenly progress; and (2) severe pre-pubertal (Wishart type) NF2- with multiple (and rapidly progressive) CNS tumours other-than-VS, which usually present first, years before VSs [vs. the classical adult (Gardner type) NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature]. Some individuals can develop unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localised to one part of the peripheral nervous system [i.e., mosaic NF2] or multiple non-VS, non-intradermal cranial, spinal and peripheral schwannomas (histologically proven) [schwannomatosis]. NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin (ERM) proteins; mosaicNF2 is due to mosaic phenomena for the NF2 gene, whilst schwannomatosis is caused by coupled germ-line and mosaic mutations either in the SMARCB1 gene [SWNTS1; MIM # 162091] or the LZTR1 gene [SWNTS2; MIM # 615670] both falling within the 22q region and the NF2 gene. Data driven from in vitro and animal studies on the merlin pathway [e.g., post-translational and upstream/downstream regulation] allowed biologically targeted treatment strategies [e.g., Lapatinib, Erlotinib, Bevacizumab] aimed to multiple tumour shrinkage and/or regression and tumour arrest of progression with functional improvement.
Population Characteristics and Progressive Disability in Neurofibromatosis Type 2. [2017]To characterize the clinical features of patients with neurofibromatosis type 2 (NF2) and determine prognostic risk factors for progressive disabilities.
An update on the CNS manifestations of neurofibromatosis type 2. [2021]Neurofibromatosis type II (NF2) is a tumor predisposition syndrome characterized by the development of distinctive nervous system lesions. NF2 results from loss-of-function alterations in the NF2 gene on chromosome 22, with resultant dysfunction of its protein product merlin. NF2 is most commonly associated with the development of bilateral vestibular schwannomas; however, patients also have a predisposition to development of other tumors including meningiomas, ependymomas, and peripheral, spinal, and cranial nerve schwannomas. Patients may also develop other characteristic manifestations such as ocular lesions, neuropathies, meningioangiomatosis, and glial hamartia. NF2 has a highly variable clinical course, with some patients exhibiting a severe phenotype and development of multiple tumors at an early age, while others may be nearly asymptomatic throughout their lifetime. Despite the high morbidity associated with NF2 in severe cases, management of NF2-associated lesions primarily consists of surgical resection and treatment of symptoms, and there are currently no FDA-approved systemic therapies that address the underlying biology of the syndrome. Refinements to the diagnostic criteria of NF2 have been proposed over time due to increasing understanding of clinical and molecular data. Large-population studies have demonstrated that some features such as the development of gliomas and neurofibromas, currently included as diagnostic criteria, may require further clarification and modification. Meanwhile, burgeoning insights into the molecular biology of NF2 have shed light on the etiology and highly variable severity of the disease and suggested numerous putative molecular targets for therapeutic intervention. Here, we review the clinicopathologic features of NF2, current understanding of the molecular biology of NF2, particularly with regard to central nervous system lesions, ongoing therapeutic studies, and avenues for further research.
Current progress in genomics and targeted therapies for neurofibromatosis type 2. [2023]Neurofibromatosis type 2 (NF2), a multiple neoplasia syndrome, is a manifestation of an impaired expression of the merlin protein, exerting inhibitory effects on cell proliferation signals due to abnormalities of the NF2 gene located on chromosome 22. About half of patients inherit a germline mutation from a parent, and nearly 60% of de novo NF2 patients are estimated to have somatic mosaicism. The development of technical methods to detect NF2 gene mutation, including targeted deep sequencing from multiple tissues, improved the diagnostic rate of mosaic NF2. With improved understanding of genetics and pathogenesis, the diagnostic criteria for NF2 were updated to assist in identifying and diagnosing NF2 at an earlier stage. The understanding of cell signaling pathways interacting with merlin has led to the development of molecular-targeted therapies. Currently, several translational studies are searching for possible therapeutic agents targeting VEGF or VEGF receptors. Bevacizumab, an anti-VEGF monoclonal antibody, is widely used in many clinical trials aiming for hearing improvement or tumor volume control. Currently, a randomized, double-masked trial to assess bevacizumab is underway. In this randomized control trial, 12 other Japanese institutions joined the principal investigators in the clinical trial originating at Fukushima Medical University. In this review, we will be discussing the latest research developments regarding NF2 pathophysiology, including molecular biology, diagnosis, and novel therapeutics.