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

Brief Title

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

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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Objective Response Rate (ORR)

Secondary Outcome

 Disease Control Rate（DCR）

Condition

Neurofibromatosis 1

Intervention

HL-085

Study Arms / Comparison Groups

 HL-085

Description:  HL-085 9mg BID

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

70

Start Date

October 18, 2021

Completion Date

October 31, 2028

Primary Completion Date

October 30, 2025

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.
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Hongqi Tian, Ph.D, 86 215201345822, [email protected]

Location Countries

China

Location Countries

China

NCT ID

NCT05331105

Organization ID

HL-085-106-II

Responsible Party

Sponsor

Study Sponsor

Shanghai Kechow Pharma, Inc.

Study Sponsor

Hongqi Tian, Ph.D, Study Chair, Shanghai Kechow Pharma, Inc.

Verification Date

April 2022