Non-small-cell lung cancer (NSCLC) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: TAGRISSO
Product Name: TAGRISSO
Pharmaceutical Form: Tablet
INN or Proposed INN: Osimertinib
CAS Number: 1421373-65-0
Current Sponsor code: Osimertinib
Other descriptive name: OSIMERTINIB
Sponsors
Universitätsklinikum Essen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures 2. Patients (male/female) must be > 18 years of age. 3. EGFRmutated NSCLC not amenable to curative treatment (surgery, curative radiochemotherapy). 4. Acquired resistance to a first- or second-generation EGFR-TKI (e.g. afatinib, erlotinib, gefitinib) following initial benefit (defined as objective response, or stable disease for at least 3 months) 5. No tumor rebiopsy available or negative result for EGFR T790M mutation status by a SoC molecular pathology test (e.g. Sanger sequencing, PCR-based genotyping, deep sequencing) of a rebiopsy of a progressive tumor lesion 6. Negative finding from EGFR T790M mutation testing in plasma-derived DNA using a SoC assay (e.g. Roche Cobas) 7. At least one tumor lesion with significant FDG uptake as determined by PET/CT scanning prior to study treatment 8. Consent to the research use of donated biological samples. 9. World Health Organization (WHO) performance status 0-2. 10. Patients must have a life expectancy = 12 weeks. 11. Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, which will be repeated on a monthly Basis, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: * Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments * Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution * Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 12. Male patients should be willing to use barrier contraception (see Restrictions, Section 3.6). 13. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. EGFR-mutated NSCLC and demonstration of the T790M resistance mutation by standard assay technology in tumor-derived or plasma-derived DNA 2. Absence of a tumor lesion with significant FDG uptake at PET/CT scanning prior to study treatment 3. Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site) 4. Previous treatment with osimertinib or any experimental or approved mutation-specific EGFR-TKI with clinical activity against the EGFR T790M resistance mutation 5. Treatment with an investigational drug within one week or five drug half-lives (whichever is longer) of the compound (3 weeks for antibodies) 6. Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 week prior) (Appendix A - Guidance regarding Potential Interactions With Concomitant Medications). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4. A list for drug interaction potential is found in section 5.1.6.4 of the osimertinib IB. 7. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior chemotherapy related neuropathy. 8. 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 the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 9. Patients with symptomatic CNS metastases who are neurologically unstable 10. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD 11. Fasting blood glucose levels above 150 mg/dl (precluding informative FDG-PET/CT scanning) 12. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: Absolute neutrophil count 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases Aspartate aminotransferase >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinaemia) or liver metastases Creatinine >1.5 times ULN concurrent with creatinine clearance 1.5 times ULN. 13. Any of the following cardiac criteria: a. Mean resting corrected QT interval (QTc using Fredericia’s formula) > 470 msec obtained from the screening clinic ECG machine-derived QTc value b. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block) c. Any factors tha
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study Osimertinib in patients with EGFR-mutated NSCLC and acquired TKI resistance who are “unknown” for EGFR T790M status due to a negative or unfeasible tumor rebiopsy, and a negative finding for EGFR T790M in a standard plasma genotyping assay;Secondary Objective: To study in patients with EGFR-mutated NSCLC and acquired TKI resistance who are “unknown” for EGFR T790M status due to a negative or unfeasible tumor rebiopsy, and a negative finding for EGFR T790M in a standard plasma genotyping assay * the predictive value of early metabolic response by FDG-PET in cycle 1 for prolonged clinical benefit defined as absence of progression for at least 4 months * the PFS of patients with early metabolic response * the overall objective response rate (including CR and PR) in all patients receiving at least 2 cycles of osimertinib * the duration of objective responses in patients with early metabolic response * the time to treatment failure of patients with early metabolic response * OS (intention-to-treat population and patients with metabolic response) * biomarkers of response and acquired resistance to first/second generation EGFR-TKI and osimertinib including targeted resequencing of a comprehensive gene panel in plasma DNA;Primary end point(s): Rate of metabolic responses as detected by FDGPET before end of cycle 1. One cycle is defined as 28 days continuous treatment.;Timepoint(s) of evaluation of this end point: Between day 15 and 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Fraction of patients with metabolic response and prolonged clinical benefit defined as absence of progression for at least 4 months * Progression-free survival (PFS) * Rate and duration of response (RECIST v. 1.1) * Time to treatment failure (TTF) under osimertinib * Overall survival (OS) of metabolic responders and intention-to-treat (ITT) population * Association of biomarkers of response and acquired resistance to first/second generation EGFR-TKI and osimertinib with PFS, TTF, ORR;Timepoint(s) of evaluation of this end point: Imaging every 8 weeks up to week 24 and every 12 weeks thereafter. Blood samples for biomarker analyses will be collected during screening and at radiological progression. | — |
Countries
Germany, Netherlands
Outcome results
None listed