Osimertinib Then Chemotherapy in EGFR-mutated Lung Cancer with Osimertinib Third-line Rechallenge
This phase II single-armed study will examine the clinical utility of retreating patients with osimertinib, in the third-line, following first-line treatment with osimertinib and second-line treatment with platinum and pemetrexed chemotherapy. The current standard of care for first-line Epidermal Growth Factor Receptor (EGFR) mutated Advanced Non-Small Cell Lung Cancer (aNSCLC) is osimertinib, followed by cytotoxic chemotherapy. The repeat of osimertinib following previous treatment failure is investigational, although supported by scientific rationale. The dosing and scheduling of osimertinib follows its use in approved settings. The investigators examine its tolerability and efficacy in this setting to ensure osimertinib is a safe third-line option for patients with Epidermal Growth Factor Receptor mutated (EGFR+) Advanced Non-Small Cell Lung Cancer(aNSCLC).
• Provision of informed consent prior to any study specific procedures
• Male or female patients of at least 18 years of age
• Pathologically proven advanced non-small cell lung cancer (i.e. stage M1 (metastasis), or earlier stages if unfit or unsuitable for radical treatment). Patients must have a tissue diagnosis of lung cancer, either by histology or cytology, however, in the event that there is insufficient tissue for molecular analysis, mutations identified in circulating tumor deoxyribonucleic acid (ctDNA) analysis will be permitted.
• Patients must have a known activating Epidermal Growth Factor Receptor (EGFR) mutation. Atypical Epidermal Growth Factor Receptor (EGRF) mutations are allowed. Atypical mutations may require sponsor approval. Exon 20 insertions will not be allowed.
• Patients must have an Eastern Cooperative Oncology Group/World Health Organisation Performance Status (ECOG/WHO-PS) of 0-3 and an expectation that they could potentially receive second-line chemotherapy
• Patients must have an expected life expectancy of at least 12 weeks
• Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential 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 amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
⁃ Women under 50 years old are consider postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) levels in the post-menopausal range for the institution
⁃ Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Male subjects should be willing to use barrier contraception
• Additional Criteria for patients enrolling after first-line progression and prior to second-line chemotherapy::
• Subjects must have complete baseline demographic data available (age at diagnosis of metastatic non-small cell lung cancer, ethnicity, smoking status, sex, history of brain metastasis) and the following must be available (if applicable):
• o Date of first dose of osimertinib, date that first-line osimertinib was permanently discontinued, date of first-line progression.
• Additional Criteria for patients enrolling at the time of third-line osimertinib rechallenge:
• Subjects must have complete baseline demographic data available (age at diagnosis of metastatic non-small cell lung cancer (NSCLC), ethnicity, smoking status, sex, history of brain metastasis) and the following must be available (if applicable):
• o Date of first dose of osimertinib, date that first-line osimertinib was permanently discontinued, date of first-line progression, date second-line chemotherapy was started, which platinum chemotherapy was given, if pemetrexed maintenance was given, date that second-line chemotherapy was permanently stopped, and date of progression on second-line treatment.
• Patients must have received platinum/ pemetrexed chemotherapy in the second-line chemotherapy
• Subjects must have measurable disease defined as at least one measurable lesion that can be accurately assessed by Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) at baseline and follow up visits.Subjects must have measurable disease defined as at least one measurable lesion that can be accurately assessed by Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) at baseline and follow up visits.