Study of HL-085 in NRAS Mutant Advanced Melanoma

• Sponsor: Shanghai Kechow Pharma, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03973151
• Collaborator: (none)
• Enrollment: 54
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 53.9
• Patients Per Site: 27
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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 .

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: HL-085	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Sep 1, 2017
• Anticipated Primary Completion Date: Mar 1, 2022
• Anticipated Study Completion Date: Mar 1, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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

2. 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)

Secondary Outcome Measures

1. 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

2. 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

3. Peak Plasma Concentration (Cmax) [Duration of the study, estimated to be approximately 24 months]

   Cmax of HL-085 following single and repeated dosing

4. 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

5. Half-life (T1/2) [Duration of the study, estimated to be approximately 24 months.]

   T1/2 of HL-085 following single and repeated dosing

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Cancer Hospital	Beijing	Beijing	China	100142
2	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China

Sponsors and Collaborators

• Shanghai Kechow Pharma, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shanghai Kechow Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT03973151
• Other Study ID Numbers: HL-085-101
• First Posted: Jun 4, 2019
• Last Update Posted: Dec 20, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Shanghai Kechow Pharma, Inc.: Melanoma; NRAS
• Additional relevant MeSH terms: Melanoma

Study Results

No Results Posted as of Dec 20, 2021