Study of HL-085 in NRAS Mutant Advanced Melanoma

Phase 1

Completed

• Conditions: Melanoma
• Interventions: Drug: HL-085

• Registration Number: NCT03973151
• Lead Sponsor: Shanghai Kechow Pharma, Inc.

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 .

Detailed Description

Not available

Study Timeline

• Study Start: 2017-09-01
• Study First Submitted: 2017-12-19
• Study First Submitted QC: 2019-06-01
• Study First Posted: 2019-06-04
• Primary Completion: 2021-01-18
• Study Completion: 2021-01-18
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-29
• Last Update Posted: 2023-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD)	DLTs within the first cycle of therapy (up to 35 days)	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)
Number of participants with adverse events	Duration of the study, estimated to be approximately 24 months.	Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 during the study period

Secondary Outcome Measures

Name	Time	Method
Half-life (T1/2)	Duration of the study, estimated to be approximately 24 months.	T1/2 of HL-085 following single and repeated dosing
Objective Response Rate (ORR) as measure of efficacy	Duration of the study, estimated to be approximately 24 months.	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
Area under the plasma concentration versus time curve (AUC)	Duration of the study, estimated to be approximately 24 months	AUC of HL-085 following single and repeated dosing
Peak Plasma Concentration (Cmax)	Duration of the study, estimated to be approximately 24 months	Cmax of HL-085 following single and repeated dosing
Time to maximum observed plasma drug concentration (Tmax)	Duration of the study, estimated to be approximately 24 months.	Tmax of HL-085 following single and repeated dosing

Trial Locations

Locations (2)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China