AFAMOSI: Efficacy and Safety of Afatinib Followed by Osimertinib Compared to Osimertinib in Patients with EGFRmutated/T790M Mutation Negative Nonsquamous NSCLC

Exclusion Criteria

• •Any investigational drug within 30 days or hormonal anticancer treatment within 2 weeks prior to randomization (continued use of anti-androgens and/or gonadorelin analogues for treatment of prostate cancer permitted)
• •T790M mutation positive tumors (by local testing)
• •Radiotherapy within 2 weeks prior to randomization, except as follows:
• •1. Palliative radiation to target organs other than chest may be allowed up to 1 week prior to randomization
• •2. Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with coordinating investigator prior to enrolling
• •Major surgery within 2 weeks before starting study treatment or scheduled for surgery during the projected course of the study
• •Known hypersensitivity to afatinib or osimertinib or the excipients of any of the trial drugs
• •History or presence of clinically relevant cardiovascular abnormalities such as
• •1. uncontrolled hypertension
• •2. congestive heart failure NYHA classification of ≥ 3
• •3. unstable angina or poorly controlled arrhythmia as determined by the investigator
• •4. Myocardial infarction within 6 months prior to randomization
• •5. Clinically important abnormalities in rhythm and conduction as measured by resting electrocardiogram (ECG) (e.g. QTc interval greater than 470 ms) or QTc interval prolongation with signs/symptoms of serious arrhythmia
• •6. Congenital long QT syndrome, congestive heart failure, electrolyte abnormalities, or intake of medicinal products that are known to prolong the QTc interval
• •Patients with a past or present medical history of
• •1. Interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD
• •2. Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug
• •3. Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhoea, malabsorption)
• •4. Known active hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier
• •5. Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 5 years and is considered to be cured
• •Pregnancy and contraception:
• •1. Women who are pregnant, nursing, or who plan to become pregnant while in the trial
• •2. Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at informed consent, for the duration of study participation and for at least 2 months for females and 4 months for males after last dose
• •Requiring treatment with any of the prohibited concomitant medications protein Inhibitors/Inductors CYP3A4/5 Inhibitors/Inductors that cannot be stopped for the duration of trial participation or concomitant St. John's Wort