Study of HL-085 in NRAS Mutant Advanced Melanoma

A Phase I/II, Single Arm, Dose Escalation and Cohort Expansion Study to Evaluate Safety, Preliminary Efficacy of HL-085 in Patients With NRAS Mutant Advanced Melanoma

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 .

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: HL-085

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed unresectable Stage III or Stage IV melanoma according to AJCC (Version 7, 2010).
2. Subjects must have NRAS mutation in melanoma.
3. 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.
4. ECOG performance status of 0-1.
5. Life expectancy ≥ 3 months.
6. Ability to take the medicine orally.
7. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HL-085; HL-085 will be administered as BID with specified dose.	Drug: HL-085; HL-085 is one MEK inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as measure of efficacy	Efficacy estimated as the Objective Response Rate (ORR) , which is the sum of Partial Response (PR) and Complete Response (CR) as determined by RECIST 1.1	Duration of the study, estimated to be approximately 24 months.
Area under the plasma concentration versus time curve (AUC)	AUC of HL-085 following single and repeated dosing	Duration of the study, estimated to be approximately 24 months
Peak Plasma Concentration (Cmax)	Cmax of HL-085 following single and repeated dosing	Duration of the study, estimated to be approximately 24 months
Time to maximum observed plasma drug concentration (Tmax)	Tmax of HL-085 following single and repeated dosing	Duration of the study, estimated to be approximately 24 months.
Half-life (T1/2)	T1/2 of HL-085 following single and repeated dosing	Duration of the study, estimated to be approximately 24 months.

Collaborators and Investigators

• Sponsor: Shanghai Kechow Pharma, Inc.
• Investigators: Study Director: Hongqi Tian, Ph.D, Shanghai Kechow Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): January 18, 2021
• Study Completion (Actual): January 18, 2021

Study Registration Dates

• First Submitted: December 19, 2017
• First Submitted That Met QC Criteria: June 1, 2019
• First Posted (Actual): June 4, 2019

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 29, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Melanoma; NRAS
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: HL-085-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No