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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| HM95573 | | HM95573 |
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
| Name | Type | Description | Interventions |
|---|
| HM95573 | Experimental | Single arm | |
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: | Completed |
| Lead Sponsor: | Hanmi Pharmaceutical Company Limited |
Last Updated
August 10, 2020
