Clinical Trials /

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

NCT03118817

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Expansion Study to Evaluate the Efficacy and Safety of HM95573 in BRAF, KRAS or NRAS Mutant Solid Cancers
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: HM-RAFI-102
  • NCT ID: NCT03118817

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
HM95573HM95573

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
HM95573ExperimentalSingle arm
  • HM95573

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (Proportion of patients with reduction in tumor burden of a predefined amount)
Time Frame: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).
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Safety and tolerability by assessing adverse events (AEs) based on CTCAE ver.4.03
Time Frame: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.
Safety Issue:
Description:
Measure:Best overall response rate
Time Frame: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).
Safety Issue:
Description:
Measure:Disease control rate
Time Frame: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).
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame: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).
Safety Issue:
Description:
Measure:Changes in molecular biomarkers
Time Frame:Screening and 15 days after first dosing
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hanmi Pharmaceutical Company Limited

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