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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
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.
Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
Shanghai, Shanghai Municipality, China
RECRUITINGObjective Response Rate (ORR)
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).
Time frame: At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days)
Disease Control Rate(DCR)
Defined as the percentage of patients who have achieved a confirmed response of CR or PR or SD
Time frame: At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days)
Duration of Overall Response(DOR)
Defined as the time from first achieved CR or PR to disease progression
Time frame: At the end of cycle 4,8,12,16,20,24,28,32.Then after every 8 cycles(each cycle is 21 days)
Progression Free survival (PFS)
Defined as the time from first dosing (C1D1) to date of first observed progression or death from any cause (whichever comes first)
Time frame: 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
Pharmacokinetic characteristics
AUC
Time frame: During the intervention
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