HL-085 in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas

The study includes 2 parts, phase IIa and IIb. Phase IIa is to evaluate the preliminary safety, pharmacokinetic characteristics and efficacy of HL-085, and to determine the recommended dose. To observe the 9mg dose level, approximately 15 patients will receive HL-085 at a dose of 9mg BID on a continuous dosing schedule(1 cycle=21 days). The investigator and sponsor will evaluate the safety and efficacy data to determine whether HL-085 9mg BID is appropriate. HL-085 12mg BID, 6mg BID, or other HL-085 dosing regimen will be observed as needed. A total of 15-35 patients will be enrolled in phase IIa. Phase IIb is to further evaluate the safety and efficacy of HL-085 in patients with NF1 and inoperable PN and is expected to enroll 35 patients.

Inclusion criteria

• Age: patients must be ≥18 years of age at the time of study entry.
• Diagnosis: Patients must have inoperable and symptomatic plexiform neurofibromas(PN), and patients must have NF1 mutation or meet at least 1 of the following NF1 diagnostic criteria:

① ≥6 cafe-au-lait macules ;

② Axillary freckling or freckling in inguinal regions;

③ ≥2 Lisch nodules (iris hamartomas);

④ A distinctive bony lesion such as dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex);

⑤ An optic pathway glioma;

⑥ First-degree relative with NF1.

• Patients must have a measurable lesion, defined as at least 3 cm in length, amenable to MRI for efficacy assessment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Patients are able to understand and voluntarily sign a written informed consent form.
• Patients must be willing and able to complete study procedures and follow-up examinations.

Exclusion criteria

• Patients who are unable to undergo MRI scans (prosthesis, prosthesis, braces, etc.) or patients with lesions that cannot be evaluated by MRI.
• Patients do not have adequate organ function.
• Patients who are unable to take drugs orally, have difficulty swallowing or anything that may lead to inadequate drug absorption.
• Prior treatment with MEK 1/2 inhibitors.
• Patients known to be allergic to the ingredients or analogues of the study drug.
• Patients with previous or current retinal diseases such as retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), central serous retinopathy (CSR), etc. (except retinopathy caused by research diseases).
• With infections or other uncontrolled disease.
• Strong CYP2C9 inhibitors or inducers within 7 days before treatment of the study drug.
• Patients who received surgery within 4 weeks or radiotherapy within 6 weeks before enrollment.
• Patients who participated in any other clinical study treatment within 4 weeks before enrollment.
• Patients treated with anti-NF1 treatment with unresolved chronic toxicity.
• Clinical judgment by the investigator that the patient should not participate in the study.