Expansion Study to Evaluate the Efficacy and Safety of HM95573 in BRAF, KRAS or NRAS Mutant Solid Cancers

A Single-arm, Open-label, Multi-center, Phase I Expansion Study Evaluating the Efficacy and Safety of HM95573 Monotherapy in Patients With BRAF, KRAS or NRAS Mutation-positive Solid Cancers

This study evaluates the anti-tumor efficacy and safety of single agent HM95573 administered in patients with solid tumors harboring mutations in either BRAF, KRAS or NRAS gene.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: HM95573

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Korea, Republic of, Seoul
  • Seoul, Korea, Republic of, 05505
    • Korea, Republic of, Seoul
  • Seoul, Korea, Republic of, 06351
    • Korea, Republic of, Seoul
  • Seoul, Korea, Republic of, 07061
    • Korea, Republic of, Seoul
  • Chungcheongbuk-do
    • Cheongju, Chungcheongbuk-do, Korea, Republic of, 28644
      • Korea, Republic of, Chungcheongbuk-do
  • Gyeonggi-do
    • Seongnam, Gyeonggi-do, Korea, Republic of, 13620
      • Korea, Republic of, Gyeonggi-do
  • Gyeongsangbuk-do
    • Daegu, Gyeongsangbuk-do, Korea, Republic of, 41404
      • Korea, Republic of, Gyeongsangbuk-do

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed solid tumor
• Confirmed mutations in either BRAF, KRAS or NRAS gene

• Eligible for biomarker analysis as follows:

  • Be able to provide an archival tumor tissue at screening.
  • Consent to undergo pre- and post-treatment tumor biopsies, provided sites of disease are easily and safely accessible
• Tumors for which standard therapy either does not exist or has proven ineffective or intolerable at study entry;
• At least one lesion (excluding brain) measureable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
• Life expectancy of ≥ 12 weeks;
• ECOG performance status score 0 or 1;
• Adequate organ function

Exclusion Criteria:

• Hematologic malignancy or double primary cancer.

• Treatment with any of the following:

  • Anticancer therapy including chemotherapy, hormonal treatment, or radiotherapy within 14 days of the first dose of study drug.
  • Investigational (not-approved) agent within 28 days or 5 fold of its half-life prior to the first dose of study drug.
  • Major surgical procedure within 28 days prior to the first dose of study drug.
  • Systemic corticosteroid (≥ 10mg prednisolone or equivalent dose of other anti-inflammatory corticosteroids) or systemic immunosuppressant within 28 days prior to the first dose of study drug or current systemic immunosuppressant which is required to be used continuously during treatment period of the study. But following treatments will be allowed: topical applications, inhaled sprays, eye drops, or local injections.
  • Treatment with nitrosourea, mitomycin, ipilimumab or other immunotherapy within 42 days prior to the first administration of study drug.
  • >5 prior anticancer therapy regimens
• Spinal cord compression, leptomeningopathy or other symptomatic or uncontrolled central nervous system or brain metastasis.

• Cardiovascular abnormalities as follow:

  • mean QTcF > 440 msec
  • Heart failure of NYHA Class III or IV
  • Heart metastasis
  • Uncontrolled serum electrolyte disturbances (hyponatremia, hypokalemia, hypocalcemia or hypomagnesemia)
  • History of acute coronary syndrome including unstable angina and myocardial infarction, uncontrolled arrhythmias (except for sinus arrhythmia and atrial fibrillation which is controlled within 30 days prior to the first dose of study drug), symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within 6 months prior to the first dose of study drug.
  • History of coronary angioplasty, coronary/peripheral artery bypass graft or stent insertion within 6 months prior to the first dose of study drug.
  • History of congenital long QT syndrome or clinically significant ≥ Grade 2 (NCI-CTCAE version 4.03) ventricular or atrial dysrhythmias.

• Ophthalmologic disorders as follows:

  • History of or evidence of retinal vein occlusion (RVO), central serous retinopathy (CSR) or neovascular macular degeneration at screening
  • Glaucoma with intraocular pressure ≥ 21 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HM95573; Single arm	Drug: HM95573; Dose: 450 mg BID Regimen: twice daily (BID), continuous dosing Duration: until progression disease or unacceptable toxicity develops

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (Proportion of patients with reduction in tumor burden of a predefined amount)	At screening and every 8 weeks from time of first dosing until date of progression, start of other anticancer therapy or death whichever came first, assessed up to study completion (around 36 months).

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability by assessing adverse events (AEs) based on CTCAE ver.4.03	All AEs occurring up to 28 days after the last administration of study drug until the start of other anti-cancer treatment, whichever comes first, will be record.
Best overall response rate	At screening and every 8 weeks from time of first dosing until date of progression, start of other anticancer therapy or death whichever came first, assessed up to study completion (around 36 months).
Disease control rate	At screening and every 8 weeks from time of first dosing until date of progression, start of other anticancer therapy or death whichever came first, assessed up to study completion (around 36 months).
Progression-free survival	At screening and every 8 weeks from time of first dosing until date of progression, start of other anticancer therapy or death whichever came first, assessed up to study completion (around 36 months).
Changes in molecular biomarkers	Screening and 15 days after first dosing

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2017
• Primary Completion (Actual): February 4, 2020
• Study Completion (Actual): February 4, 2020

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: April 16, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Actual): August 10, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: HM-RAFI-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No