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

Shanghai Kechow Pharma, Inc.2 sites in 1 country42 target enrollmentSeptember 1, 2017

ConditionsMelanoma

InterventionsHL-085

DrugsHL-085

Overview

Phase: Phase 1
Intervention: HL-085
Conditions: Melanoma
Sponsor: Shanghai Kechow Pharma, Inc.
Enrollment: 42
Locations: 2
Primary Endpoint: Maximum tolerated dose (MTD)
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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 .

Registry

clinicaltrials.gov

Start Date

September 1, 2017

End Date

January 18, 2021

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Kechow Pharma, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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-
•Life expectancy ≥ 3 months.
•Ability to take the medicine orally.
•Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

•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.

Arms & Interventions

HL-085

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

Intervention: HL-085

Outcomes

Primary Outcomes

Maximum tolerated dose (MTD)

Time Frame: 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

Time Frame: 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 Outcomes

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