HLX-1502 for Neurofibromatosis

(INSPIRE-NF1 Trial)

Recruiting at 13 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

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called HLX-1502 for individuals with neurofibromatosis type 1 (NF1), a condition that causes tumor growth on nerves. The trial aims to assess the treatment's effectiveness and tolerability. It targets those aged 16 and older with progressively worsening or painful tumors that impact daily life, such as causing nerve problems or significant discomfort. Participants will take the treatment as a pill three times a day for up to 24 cycles, with each cycle lasting 28 days. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that HLX-1502 is likely to be safe for humans?

Research has shown that HLX-1502 is generally safe based on previous studies. Patients who took HLX-1502 tolerated it well, with no major reports of serious side effects. The treatment is also being developed for other types of neurofibromatosis, indicating confidence in its safety. As this is a Phase 2 trial, earlier tests suggested it is safe enough for study in more people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neurofibromatosis?

Unlike the standard treatments for neurofibromatosis, which primarily focus on managing symptoms through surgery or radiation, HLX-1502 acts directly on the molecular pathways involved in tumor growth. Researchers are excited about HLX-1502 because it is administered orally, offering a potentially less invasive option compared to traditional methods. Additionally, its novel mechanism targets specific tumor mechanisms, which might lead to better control of the disease and possibly improved outcomes for patients.

What evidence suggests that HLX-1502 might be an effective treatment for neurofibromatosis?

Research has shown that HLX-1502, the treatment under study in this trial, may help treat neurofibromatosis type 1 (NF1) with plexiform neurofibromas (PN). An earlier study found that 41% of adults and 52% of children experienced positive results, such as tumor shrinkage or symptom relief. This treatment aims to slow the growth of these nerve tumors, which are common in NF1. These early findings suggest that HLX-1502 could effectively manage symptoms and reduce tumor growth for people with NF1. ^{1 2 4 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

Citations

1. healx.ai healx.ai/healx-announces-first-patient-dosed-in-phase-2-trial-evaluating-hlx-1502-for-the-treatment-of-neurofibromatosis-type-1/

Healx Announces First Patient Dosed in Phase 2 Trial ... INSPIRE-NF1 is a Phase 2, open-label, single-arm study evaluating the safety and efficacy of HLX-1502 in NF1 patients with plexiform ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06541847

NCT06541847 | A Phase 2, Open-Label Study to Evaluate ... 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.

3. hopkinsmedicine.org hopkinsmedicine.org/neurology-neurosurgery/specialty-areas/neurofibromatosis/clinical-trials

Neurofibromatosis Clinical Trials This is a phase 2, multi-center, open-label, single-arm study evaluating the safety and efficacy of HLX-1502 in people with NF1 with plexiform neurofibromas and ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/healx-neurofibromatosis-trial/

Healx doses first subject in Phase II NF1 therapy trial Healx has dosed the first subject in the Phase II INSPIRE-NF1 trial to assess the efficacy and safety of HLX-1502 in individuals with NF1.

5. medicine.iu.edu medicine.iu.edu/blogs/neuroscience/iu-neurologist-research-leads-to-first-fda-approved-drug

IU neurologist's research leads to first FDA-approved drug to ... The overall results of this multicenter, single-arm study were successful as 41% of adult patients (out of 58) and 52% of pediatric patients ( ...

6. ctf.org ctf.org/news/healx-to-receive-investment-from-childrens-tumor-foundation-to-advance-neurofibromatosis-type-1-treatments/

Healx to receive investment from Children's ... ... data that suggest a favorable safety profile. Healx plans to develop HLX-1502 for both plexiform and cutaneous subtypes of NF1. Financial ...

7. synapse.patsnap.com synapse.patsnap.com/drug/417e0a92a1a74673964c7da29a65bef6

HLX-1502 - Drug Targets, Indications, Patents A Phase 2, Open-Label, Single Arm, Non-Controlled, Single-Stage Study to Evaluate the Safety and Effects of HLX-1502 in Patients With Plexiform Neurofibroma ...