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

• ClinicalTrials.gov Identifier: NCT03118817
• Recruitment Status: Completed
• First Posted: April 18, 2017
• Last Update Posted: August 10, 2020
• Sponsor: Hanmi Pharmaceutical Company Limited
• Information provided by (Responsible Party): Hanmi Pharmaceutical Company Limited

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Drug: HM95573	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 65 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 19, 2017
• Actual Primary Completion Date: February 4, 2020
• Actual Study Completion Date: February 4, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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). ]

Secondary Outcome Measures :

1. 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. ]
2. 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). ]
3. 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). ]
4. 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). ]
5. Changes in molecular biomarkers [ Time Frame: Screening and 15 days after first dosing ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

Korea, Republic of

Korea, Republic of, Chungcheongbuk-do

Cheongju, Chungcheongbuk-do, Korea, Republic of, 28644

Korea, Republic of, Gyeonggi-do

Seongnam, Gyeonggi-do, Korea, Republic of, 13620

Korea, Republic of, Gyeongsangbuk-do

Daegu, Gyeongsangbuk-do, Korea, Republic of, 41404

Korea, Republic of, Seoul

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

Sponsors and Collaborators

Hanmi Pharmaceutical Company Limited

More Information

• Responsible Party: Hanmi Pharmaceutical Company Limited
• ClinicalTrials.gov Identifier: NCT03118817
• Other Study ID Numbers: HM-RAFI-102
• First Posted: April 18, 2017
• Last Update Posted: August 10, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No