Clinical trial NCT05217303: HL-085 in NRAS-mutated Advanced Melanoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Keywords: HL-085
MEK inhibitor
NRAS mutation
advanced melanoma
Lead sponsor: Shanghai Kechow Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: objective response rate (ORR)
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: progression-free survival (PFS)
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Oncology Hospital
state: Beijing
Study officials:
affiliation: Shanghai Kechow Pharma, Inc.
name: Hongqi Tian, Ph.D
role: STUDY_DIRECTOR
References: