Study of HL-085 in Patients With Advanced Solid Tumor Tumors

NCT04683354 | Completed Phase 1 FDA Drug

• 1 other identifier: HL-085-US-102
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

Brief Summary

The investigational product (IP) HL-085 is an adenosine triphosphate-noncompetitive mitogen activated protein kinase (MEK) inhibitor with a strong selective anti-tumor activity, with a much lower dose than selumetinib. It has been shown strong anti-tumor activities in preclinical studies to treat solid tumors, e.g., melanoma, non-small cell lung cancer, colon cancer and other malignancies with RAF and RAS mutations. Kechow has completed phase I dose escalation study to test HL-085 in patients with advanced NRAS mutated melanoma in China. The tested doses were 0.5 mg, 1mg, 2mg, 3mg, 4mg, 6mg, 9mg, 12mg, 15mg and 18mg BID oral administration and there was no dose-limiting toxicity (DLT) identified. All patients tolerated the study drug reasonably well. This study is a Phase I, open-label, dose escalation study to evaluate tolerability, safety, pharmacokinetic (PK) and preliminary antitumor activities of HL-085 in US patients with advanced solid tumors. The objective of the dose escalation is to evaluate safety and tolerability of selected TID and BID dose regimens in US patient population with advanced solid tumor and establish the Recommended Phase 2 Dose (RP2D). The starting dose for this trial is 12 mg daily oral administration. Three selected daily doses - 12 mg (4mg TID, 6mg BID), 18 mg (6mg TID, 9 mg BID), and 24 mg (8 mg TID, 12 mg BID) will be tested in this study to assess safety and tolerability of HL-085 at the 3 selected dose levels in US patient population with advanced solid tumors.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (4)

• Characterize the safety profile of the study drug at 3 dose levels in terms of number of treatment emergent events assessed by CTCAE v5.0., abnormal clinical laboratory and electrocardiograms findings (i.e. QT and QTc intervals).

  7 months (6 months treatment + 1 month follow-up)

• Cmax: the maximum plasma concentration of HL-085 or metabolite(s);

  1 month (Cycle 1 Day 1-31)

• Tmax: the time of Cmax;

  1 month (Cycle 1 Day 1-31)

• Area under the curve at steady state: a measure of the exposure to HL-085 or metabolite(s) at steady state.

  1 month (Cycle 1 Day 1-31)

Secondary Outcomes (1)

• Evaluate the efficacy of the study drug in terms of overall response rate, progression-free survival. ORR is the proportion of patients with a best overall response of complete response (CR) or partial response (PR), as assessed per RECIST v1.1.

  7 months (6 months treatment + 1 month follow-up)

Study Arms (1)

Dose Escalation

EXPERIMENTAL

There are 3 cohorts for the dose escalation study. Six subjects each cohort will receive oral administration of HL-085 capsules at three daily dose levels (12 mg, 18 mg and 24 mg). Three subjects of each cohort will receive TID and 3 subjects will receive BID dose regimen. Dose escalation can occur after 6 patients have completed 28 days of treatment and no or 1 DLT is identified.

Drug: HL-085

Interventions

HL-085 DRUG

HL-085 is a MEK inhibitor with potential indication for cancers. It will be given twice or three times daily continuously in the study until disease progression; or the risks outweigh the benefits, if the subject continues study treatment; or subjects with poor compliance; or subjects need to receive or have already started alternative antitumor drugs; or Subjects who need to receive or have already started alternative any other concomitant medication and/or treatment, which would significantly impact their safety; or interruption of IP administration for more than 14 days due to IP-related AEs.

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any clinical trial procedures
• Aged 18 years or over.
• Must have a pathologically documented solid tumor(s) that has relapsed from, or is refractory to standard treatment, or unable to tolerate toxicities from the SOC/available treatments, or for which no standard treatment is available.
• Must have at least one measurable lesion as defined by RECISTv1.1 criteria for solid tumors.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Life expectancy ≥3 months (as judged by the Investigator).
• Must have adequate hematologic function (no blood transfusion and growth factor support for ≥14 days), adequate hepatic and renal function, and some key lab test results meeting the following laboratory values within 7 (+/-2) days before first dosing.
• Must have the willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.

You may not qualify if:

• Have biological, chemotherapy, immunotherapy or radiotherapy less than 4 weeks prior to starting the study treatment.
• Have undergone or plan to have major surgery (except for tumor biopsy) or experienced severe trauma ≤28 days prior to starting the study treatment.
• Have active central nervous system lesion (i.e., imaging instability and neurologically unstable). Note: patients who have received stereotactic radiotherapy or surgical treatment for brain tumor can be included after 3 months of procedure without symptoms.
• Previous or history of second malignancy within 3 years prior to study treatment except for curatively treated.
• Prior therapy with MEK-inhibitor with severe toxicity causing permanent damage from it, such as ocular, cardiac, pulmonary, etc. disorders and illness.
• History of any of the following within 6 months prior to Screening:
• Myocardial infarction.
• Unstable angina.
• Coronary artery bypass graft.
• Coronary angioplasty or stenting.
• Chronic heart failure (New York Heart Association Grade ≥2).
• Ventricular arrhythmias requiring continuous therapy.
• Supraventricular arrhythmias, including atrial fibrillation, which are uncontrolled.
• Uncontrolled hypertension despite optimal medication management (per Investigator's assessment)
• Cerebrovascular accidents including transient ischemic attack, or pulmonary embolism.

Sponsors & Collaborators

• Kechow Pharma, Inc.: lead

Study Sites (5)

CCARE

San Marcos, California, 92069, United States

Location

Comprehensive Cancer Centers

Las Vegas, Nevada, 89169, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

SCRI

Nashville, Tennessee, 37203, United States

Location

Oncology Consultants

Houston, Texas, 77030, United States

Location

Study Officials

• Hongqi Tian, PhD

  Kechow Pharma, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 24, 2020
• Study Start: December 23, 2020
• Primary Completion: September 15, 2022
• Study Completion: December 8, 2022
• Last Updated: February 13, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)