HLX-1502 for Neurofibromatosis

(INSPIRE-NF1 Trial)

Recruiting at 7 trial locations

Overseen By Karen Cole-Plourde

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Healx Limited

Must not be taking: MEK-inhibitors, TKI drugs

Disqualifiers: NF1-related tumors, Cardiovascular disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

20 Participants Needed

Trial Summary

Will 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.

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. ^{1 2 3 4 5}

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.

Research Team

Miriam Bornhorst

Principal Investigator

Lurie's Children's Hospital

Michael Fisher

Principal Investigator

Children's Hospital of Philadelphia

Kathryn Nevel

Principal Investigator

Indiana University

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 am 16 years or older and have considered or tried MEKi therapy.

I weigh at least 49 kg.

I can do most of my daily activities by myself.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take an oral dose of HLX-1502 three times a day for 12 cycles, with each cycle lasting 28 days

48 weeks

Extended Treatment

Participants with partial response or stable disease can continue therapy for an additional 12 cycles

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• HLX-1502

Trial Overview 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.

Participant Groups

Group I: HLX-1502 Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

Healx Limited

Lead Sponsor

Trials

3

Recruited

30+

Findings from Research

In a study of 807 patients with neurofibromatosis type 2 (NF2), the median age of onset was 24 years, and the most common symptoms included bilateral cranial nerve tumors and hearing loss, highlighting the diverse clinical features of NF2.

Significant risk factors for progressive disability in NF2 patients included being diagnosed before age 25, having a family history of NF2, and experiencing specific neurologic deficits like hearing loss and facial paresis, indicating that early intervention may be crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Characteristics and Progressive Disability in Neurofibromatosis Type 2. Iwatate, K., Yokoo, T., Iwatate, E., et al.[2017]

Neurofibromatosis type II (NF2) is caused by mutations in the NF2 gene, leading to the development of various tumors, primarily bilateral vestibular schwannomas, and has a highly variable clinical course among patients.

Currently, there are no FDA-approved systemic therapies targeting the underlying biology of NF2, and management mainly involves surgical resection of tumors; however, new insights into its molecular biology are revealing potential therapeutic targets for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the CNS manifestations of neurofibromatosis type 2. Coy, S., Rashid, R., Stemmer-Rachamimov, A., et al.[2021]

Neurofibromatosis type 2 (NF2) is caused by mutations in the NF2 tumor suppressor gene on chromosome 22, leading to conditions like bilateral vestibular schwannomas and other tumors, with about 50% of cases arising from new mutations.

The clinical presentation of NF2 varies significantly, with some patients experiencing severe symptoms early in life while others have a milder form that develops later, highlighting the importance of genetic testing and personalized care strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Neurofibromatosis type 2 (central neurofibromatosis or bilateral acoustic neuromas, vestibular schwannomas): from phenotype to gene]. Sabol, Z., Kipke-Sabol, L., Miklić, P., et al.[2009]

Neurofibromatosis type 2 (NF2) is a genetic disorder caused by mutations in the NF2 gene, leading to the development of various tumors, including vestibular schwannomas and meningiomas, with distinct clinical presentations in children and adults.

Research on the merlin protein pathway has led to targeted treatment strategies using drugs like Lapatinib and Bevacizumab, which aim to shrink tumors and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. Ruggieri, M., Praticò, AD., Serra, A., et al.[2019]

Neurofibromatosis type 2 (NF2) is linked to mutations in the NF2 gene, affecting the merlin protein, which normally inhibits cell growth; advancements in genetic testing have improved the diagnosis of this condition, especially in cases of somatic mosaicism.

Current research is focused on targeted therapies, particularly using bevacizumab, an anti-VEGF monoclonal antibody, which is being tested in a randomized trial across multiple institutions for its potential to improve hearing and control tumor growth in NF2 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current progress in genomics and targeted therapies for neurofibromatosis type 2. Hiruta, R., Saito, K., Bakhit, M., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Population Characteristics and Progressive Disability in Neurofibromatosis Type 2. [2017]

2. Germany pubmed.ncbi.nlm.nih.gov

An update on the CNS manifestations of neurofibromatosis type 2. [2021]

3. Croatia pubmed.ncbi.nlm.nih.gov

[Neurofibromatosis type 2 (central neurofibromatosis or bilateral acoustic neuromas, vestibular schwannomas): from phenotype to gene]. [2009]

4. Italy pubmed.ncbi.nlm.nih.gov

Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

Current progress in genomics and targeted therapies for neurofibromatosis type 2. [2023]