NCT03973151

Brief Summary

This is a phase I/II, open-label, dose escalation study to evaluate tolerability, safety, pharmacokinetics and efficacy in patients with NRAS mutant advanced melanoma .

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Sep 2017

Typical duration for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2017

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

December 19, 2017

Completed
1.5 years until next milestone

First Posted

Study publicly available on registry

June 4, 2019

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 18, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 18, 2021

Completed
Last Updated

May 31, 2023

Status Verified

May 1, 2023

Enrollment Period

3.4 years

First QC Date

December 19, 2017

Last Update Submit

May 29, 2023

Conditions

Melanoma

Keywords

MelanomaNRAS

Outcome Measures

Primary Outcomes (2)

  • Number of participants with adverse events

    Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 during the study period

    Duration of the study, estimated to be approximately 24 months.

  • Maximum tolerated dose (MTD)

    The dose level immediately below the dose level at which ≥ 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity (DLT)

    DLTs within the first cycle of therapy (up to 35 days)

Secondary Outcomes (5)

  • Objective Response Rate (ORR) as measure of efficacy

    Duration of the study, estimated to be approximately 24 months.

  • Area under the plasma concentration versus time curve (AUC)

    Duration of the study, estimated to be approximately 24 months

  • Peak Plasma Concentration (Cmax)

    Duration of the study, estimated to be approximately 24 months

  • Time to maximum observed plasma drug concentration (Tmax)

    Duration of the study, estimated to be approximately 24 months.

  • Half-life (T1/2)

    Duration of the study, estimated to be approximately 24 months.

Study Arms (1)

HL-085

EXPERIMENTAL

HL-085 will be administered as BID with specified dose.

Drug: HL-085

Interventions

HL-085DRUG

HL-085 is one MEK inhibitor.

HL-085

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically confirmed unresectable Stage III or Stage IV melanoma according to AJCC (Version 7, 2010).
  • Subjects must have NRAS mutation in melanoma.
  • Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment. Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment.
  • ECOG performance status of 0-1.
  • Life expectancy ≥ 3 months.
  • Ability to take the medicine orally.
  • Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

  • Prior therapy with a MEK-inhibitor
  • Patients with known hypersensitivity to study drug ingredients or their analogues.
  • Active central nervous system (CNS) lesion.
  • ECG QTcB≥480msec in screening, or history of congenital long QT syndrome.
  • Subjects with bleeding symptoms at Grade 3 (NCI-CTCAE v4.03) within 4 weeks prior to starting study treatment.
  • Uncontrolled concomitant diseases or infectious diseases.
  • Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.).
  • History of HIV,HCV,HBV infection.
  • Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded.
  • Serum HCG test is positive.
  • Other conditions that influence the results and increase the risk of study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Location

Related Publications (1)

  • Wang X, Luo Z, Chen J, Chen Y, Ji D, Fan L, Chen L, Zhao Q, Hu P, Sun P, Jia Z, Guo J, Si L. First-in-human phase I dose-escalation and dose-expansion trial of the selective MEK inhibitor HL-085 in patients with advanced melanoma harboring NRAS mutations. BMC Med. 2023 Jan 4;21(1):2. doi: 10.1186/s12916-022-02669-7.

    PMID: 36600247DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Hongqi Tian, Ph.D

    Shanghai Kechow Pharma, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 19, 2017

First Posted

June 4, 2019

Study Start

September 1, 2017

Primary Completion

January 18, 2021

Study Completion

January 18, 2021

Last Updated

May 31, 2023

Record last verified: 2023-05

Locations

CN(2)