hl-085 in adults with neurofibromatosis type 1 (nf1) and inoperable plexiform neurofibromas

Conditions: Neurofibromatosis 1; Plexiform Neurofibromas

Summary: this is a multi-center, open-label, single-arm phase ii study to evaluate the efficacy and safety of hl-085 in the treatment of adult participants with neurofibromatosis type 1 (nf1) and inoperable plexiform neurofibromas(pn)

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.

Eligibility criteria:
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.