A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients with EGFR Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
- Conditions
- Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003106-28-GB
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 30
For inclusion in the study, patients must fulfill all of the following criteria.
1. Signed Written Informed Consent
? Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses. For inclusion in optional genetic and/or biomarker research, patients must provide informed consent for the research.
2. Age and Sex
? At least 20 years of age and older or adult men and women for each country.
? Females should agree to use adequate contraceptive measure, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of following criteria at screening:
- Post-menopausal defined as aged more than 50 years and ameorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
- Women under 50 years old would be considered postmenopausal if they have been ameorrhoeic for at least 12 months following cessation of exogenous hormonal treatment, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in postmenopausal range for the institution.
? Male patients who have not undergone a vasectomy must agree to use barrier contraception i.e. condoms, and refrain from donating sperm until 3 months after last drug is taken.
? During the study, and for 3 months after receiving the last dose of study drug, female patients must agree not to donate eggs (ova, oocytes) and male patients must agree not to donate sperm for the purposes of assisted reproduction.
3. Target disease
? Parts A, B and C only: Histologically or cytologically(i.e., pleural effusion, ascites cases) confirmed diagnosis of NSCLC with single activating EGFR mutations (L858R or Exon19Del or G719X or L861Q). EGFR mutation status should have been determined using well-validated and robust methodology which has been approved by the regulatory authority. In the country where diagnosis of EGFR mutation does not need to use regularity approved kit, well-validated methodology will be used.
- In Part D: Patients outside Korea with histologically or cytologically (ie, using pleural effusion, ascites) confirmed NSCLC with previously diagnosed EGFRm+, and who have had progressive disease on prior EGFR-TKI therapy.
? Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 3 months.
? Patients who have at least one measurable extracranial lesion, not previously irradiated and not chosen for biopsy during the study screening period or one measurable lesion that has passed 14 days or more after biopsy, that can be accurately measured at baseline as = 10mm in the longest diameter (except lymph nodes which must have short axis = 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), are suitable for accurate repeated measurement.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
Patients must not enter the study if any of the following exclusion criteria are fulfilled.
1. Intervention with any the following:
? An unapproved investigational product from another clinical study within 30 days of the first dose of study treatment
? Treatment with an EGFR TKIs within 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment or other investigational products within approved indication of marketed product
? Any cytotoxic chemotherapy or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen within 14 days of the first dose of study treatment
? Major surgery (excluding for vascular access) within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study
? Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment with the exception of patients receiving radiation to more than 30% of the bone marrow marrow which must be completed within 4 weeks of the first dose of study treatment
? Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of YH25448) medications or herbal supplements known to be inhibitors or inducers of CYP3A4
? Any unresolved toxicities from prior therapy, greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting 1st study treatment with the exception of alopecia
2. Medical History and Concurrent Disease
? Symtomatic spinal cord compression (if steroid treatment is not required within at least 2 weeks prior to the start of the study treatment then the patient may be enrolled)
? Brain metastases with symptomatic and/or requiring emergency treatment
? Intracranial hemorrhage with symptomatic and/or requiring treatment
? CNS complications that require urgent neurosurgical intervention
? Leptomeningeal metastasis prior to study treatment
? Past medical history of interstitial lung disease (ILD), drug-induced IDL, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
? Carcinoma besides NSCLC requiring treatment or any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator’s opinion makes it undesirable for the patient to participate in trial or which would jeopardise compliance with the protocol. Screening for chronic condition is not required
? Any cardiovascular disease as followed,
a) History of symptomatic CHF or serious cardiac arrhythmia requiring treatment
b) History of myocardial infarction or unstable angina within 6 months of the first dose of study treatment
c) LVEF <50%
? Active hepatitis with HbsAg+ or anti-HCV Ab+, confirmed positive HIV test results
? Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of study medication
? History of hypersensitivity to active or inactive excipients of YH25448 or drugs with a similar chemical structure or class to YH25448
? Clinically significant chronic infection or significant medical or psychiatric illness
? Judgment by investigators that the patient should not participate in the study if the patient is unlikely to comply with study procedure, restricti
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method