HL-085 in NRAS-mutated Advanced Melanoma

A Single-arm, Multi-center Phase II Clinical Study to Evaluate the Efficacy and Safety of HL-085 in Advanced Melanoma Patients With NRAS Mutation

This was an open-label, single-arm, multi-center phase II clinical study, aimed at investigating the efficacy and safety of HL-085 capsule in the treatment of advanced melanoma patients with NRAS mutation.

Study Overview

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

Detailed Description

This was an open-label, single-arm, multi-center phase II clinical study, aimed at investigating the efficacy and safety of HL-085 capsule in the treatment of advanced melanoma patients with NRAS mutation. The primary objective was to evaluate the objective response rate (ORR) of oral HL-085 capsule in patients with advanced melanoma harboring NRAS mutation. The secondary objectives were to evaluate the progression-free survival (PFS), disease control rate (DCR), duration of remission (DOR), 1-year survival rate, overall survival (OS) and safety.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhimei Zhu, Master; Phone Number: 86 215201345822; Email: zhuzm@kechowpharma.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China
      • Beijing Oncology Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 Years or older (male or female).
• Patients have histologically or cytologically confirmed Unresectable stage III or IV melanoma;
• Able to provide the genetic test report with documented NRAS mutation at baseline.
• At least one target lesion as per RECIST v1.1 criteria.
• Previous chemotherapy, immunotherapy, or radiotherapy must have been completed at least 4 weeks prior to study drug administration, and all related toxic reactions (with the exception of alopecia) must have been resolved (to Grade ≤1 or baseline) prior to study drug administration.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy > 3 months.
• No major surgery (excluding baseline tumor biopsy) or major trauma occurred at least 14 days prior to study drug administration.

Exclusion Criteria:

• Patients with active central nervous system (CNS) lesions (i.e., radiological evidence of instability, symptomatic lesions) should be excluded. Note: Patients receiving stereotactic brain radiotherapy or surgery who have shown no brain disease progression over a period of 3 months or longer are eligible for inclusion.
• Patients had received any other study treatment within the past 4 weeks prior to study drug administration.
• Inability to swallow the capsule, refractory nausea and vomiting, malabsorption, extracorporeal biliary shunt, or any small intestinal resection that would preclude adequate absorption of the study drug.
• ECG QTcB ≥ 480 msec (adjusted by Bazetts formula) during screening, or a history of congenital long QT syndrome.
• Bleeding symptoms of Grade 3 as defined by the National Cancer Institute General Terminology Standard for Adverse Events (NCI CTCAE V5.0) within the past 4 weeks prior to study initiation.
• One of the following situations occurs within the past 6 months prior to administration of study drug: myocardial infarction, severe/unstable angina, coronary artery/peripheral artery bypass grafting, symptomatic congestive heart failure, serious arrhythmia, uncontrolled hypertension, cerebrovascular accident, or transient ischemic attack, or symptomatic pulmonary embolism.
• Current use of other anti-cancer drugs (hormone therapy was acceptable).
• Uncontrolled concomitant diseases or infectious diseases.
• Patients have retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED) or other retinal diseases previously or currently.

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; 12 mg BID HL-085	Drug: HL-085; HL-085 capsule administered orally twice daily (BID) in a 21-day treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR)	To evaluate the objective response rate (ORR) of patients with advanced melanoma harboring NRAS mutation. ORR by RECIST v1.1 following treatment with HL-085	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival (PFS)	To evaluate the progression-free survival (PFS), disease control rate (DCR), duration of remission (DOR) of patients with advanced melanoma harboring NRAS mutation after HL-085 treatment.	through study completion, an average of 1 year

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): November 2, 2020
• Primary Completion (Actual): February 19, 2023
• Study Completion (Actual): February 20, 2023

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): February 1, 2022

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: MEK inhibitor; advanced melanoma; NRAS mutation; HL-085
• 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-II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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