Clinical trial NCT05331105: HL-085 in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neurofibromatosis 1
Plexiform Neurofibromas
Lead sponsor: Shanghai Kechow Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-15
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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)

Detailed description: 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days)
Secondary outcomes:
measure: Disease Control Rate（DCR）
timeFrame: At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days)
measure: Duration of Overall Response（DOR）
timeFrame: At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days)
measure: Progression Free survival (PFS)
timeFrame: From date of dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
measure: Pharmacokinetic characteristics
timeFrame: During the intervention
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Kechow Pharma, Inc.
name: Hongqi Tian, Ph.D
role: STUDY_CHAIR
References: