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

Primary Purpose

Neurofibromatosis 1, Plexiform Neurofibromas

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

HL-085

About this trial

This is an interventional treatment trial for Neurofibromatosis 1

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HL-085

Arm Description

HL-085 9mg BID

Outcomes

Primary Outcome Measures

Objective 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).

Secondary Outcome Measures

Disease Control Rate（DCR）

Defined as the percentage of patients who have achieved a confirmed response of CR or PR or SD

Duration of Overall Response（DOR）

Defined as the time from first achieved CR or PR to disease progression

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)

Pharmacokinetic characteristics

AUC

Full Information

NCT ID

NCT05331105

First Posted

March 15, 2022

Last Updated

May 29, 2023

Sponsor

Shanghai Kechow Pharma, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05331105

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 18, 2021 (Actual)

Primary Completion Date

October 30, 2025 (Anticipated)

Study Completion Date

October 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Kechow Pharma, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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)

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neurofibromatosis 1, Plexiform Neurofibromas

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HL-085

Arm Type

Experimental

Arm Description

HL-085 9mg BID

Intervention Type

Drug

Intervention Name(s)

HL-085

Intervention Description

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.

Primary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

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)

Secondary Outcome Measure Information:

Title

Disease Control Rate（DCR）

Description

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)

Title

Duration of Overall Response（DOR）

Description

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)

Title

Progression Free survival (PFS)

Description

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

Title

Pharmacokinetic characteristics

Description

AUC

Time Frame

During the intervention

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhimei Zhu, Master

Phone

86 215201345822

zhuzm@kechowpharma.com

First Name & Middle Initial & Last Name or Official Title & Degree

Hongqi Tian, Ph.D

tianhq@kechowpharma.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hongqi Tian, Ph.D

Organizational Affiliation

Shanghai Kechow Pharma, Inc.

Official's Role

Study Chair

Facility Information:

Facility Name

Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200011

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Qingfeng Li, M.D.

Phone

13301990666

dr.liqingfeng@shsmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

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

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