HL-085 in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas
Study Details
Study Description
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HL-085 HL-085 9mg BID |
Drug: HL-085
IIa: HL-085 capsule 9mg administered orally twice daily in a continuous 21-day treatment cycle. If required, dosing schedule can be adjusted to 12mg BID, 6mg BID, or other dosage regimens.
IIb: HL-085 at the recommended dose or dosage regimen.
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) [At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days)]
To assess the efficacy of HL-085 on the tumor volume (plexiform neurofibromas) using volumetric MRI per REiNS criteria. ORR is defined as the percentage of patients who have achieved a confirmed Partial Responses (PR) or Complete Responses (CR).
Secondary Outcome Measures
- Disease Control Rate（DCR） [At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days)]
Defined as the percentage of patients who have achieved a confirmed response of CR or PR or SD
- Duration of Overall Response（DOR） [At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days)]
Defined as the time from first achieved CR or PR to disease progression
- Progression Free survival (PFS) [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]
Defined as the time from first dosing (C1D1) to date of first observed progression or death from any cause (whichever comes first)
- Pharmacokinetic characteristics [During the intervention]
AUC
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age: patients must be ≥18 years of age at the time of study entry.
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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.
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Patients must have a measurable lesion, defined as at least 3 cm in length, amenable to MRI for efficacy assessment.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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Patients are able to understand and voluntarily sign a written informed consent form.
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Patients must be willing and able to complete study procedures and follow-up examinations.
Exclusion Criteria:
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Patients who are unable to undergo MRI scans (prosthesis, prosthesis, braces, etc.) or patients with lesions that cannot be evaluated by MRI.
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Patients do not have adequate organ function.
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Patients who are unable to take drugs orally, have difficulty swallowing or anything that may lead to inadequate drug absorption.
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Prior treatment with MEK 1/2 inhibitors.
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Patients known to be allergic to the ingredients or analogues of the study drug.
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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).
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With infections or other uncontrolled disease.
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Strong CYP2C9 inhibitors or inducers within 7 days before treatment of the study drug.
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Patients who received surgery within 4 weeks or radiotherapy within 6 weeks before enrollment.
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Patients who participated in any other clinical study treatment within 4 weeks before enrollment.
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Patients treated with anti-NF1 treatment with unresolved chronic toxicity.
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Clinical judgment by the investigator that the patient should not participate in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine | Shanghai | Shanghai | China | 200011 |
Sponsors and Collaborators
- Shanghai Kechow Pharma, Inc.
Investigators
- Study Chair: Hongqi Tian, Ph.D, Shanghai Kechow Pharma, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HL-085-106-II