D-0316 Versus Icotinib in Patients With Locally Advanced or Metastatic EGFR Sensitising Mutation Positive NSCLC

A Phase II/III, Open-Label, Randomised Study to Assess the Safety and Efficacy of D-0316 Versus Icotinib as First Line Treatment in Patients With EGFR Sensitising Mutation, Locally Advanced or Metastatic NSCLC

To assess the efficacy and safety of D-0316 versus Icotinib, a standard of care epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), in patients with locally advanced or Metastatic Non Small Cell Lung Cancer (NSCLC).

This is a Phase II/III, open-label, randomised study assessing the efficacy and safety of D-0316 (70 mg once daily for 21 days, then increased to 100 mg once daily, orally) versus Icotinib (125 mg three times daily, orally) in patients with locally advanced or metastatic NSCLC that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naive and eligible for first-line treatment with an EGFR-TKI.

Inclusion Criteria:

• Male or female, 18 years of age or older.
• Pathologically confirmed adenocarcinoma of the lung, with locally advanced or metastatic disease and not amenable to curative surgery or radiotherapy (stage IIIB, IIIC or IV disease based on the eighth edition of the American Joint Committee on Cancer (AJCC) TNM classification). Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
• Patients must be treatment-naive for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with icotinib. Prior adjuvant and neo-adjuvant therapy (except for EGFR-TKI) is permitted if have been completed at least 6 months prior to initiation of study drug.
• The tumour tissues harbour one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations, assessed by central laboratory.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Predicted survival ≥ 3 months
• At least 1 measurable tumor lesion as per RECIST v1.1
• Agree to use effective contraception during the study period and for at least 3 months after completion of the study treatment
• Provision of informed consent prior to any study procedure.

Exclusion Criteria:

• Evidence of any concurrent or history of malignancy (except for clinically cured in situ cervix carcinoma, basal cell or squamous epithelial skin cancer, thyroid papillary carcinoma).
• Prior treatment with EGFR-TKI.
• Prior treatment with any systemic anti-cancer therapy for locally advanced or metastatic NSCLC including chemotherapy, biological therapy, immunotherapy, and etc.
• Previous therapeutic clinical trial with 4 week of the first dose of study drug.
• Previous traditional chinese medicine with an anti-cancer indication within 2 weeks of the first dose of study drug.
• Previous major surgery (except for tooth extraction) within 4 weeks of the first dose of study drug, planing to have major surgery during study.
• Symptoms or signs worsened within 2 weeks before screening.
• Any unresolved toxicities from prior treatment greater than NCI CTCAE v4.03 grade 2 or higher, with the exception of hair loss.
• Spinal cord compression, symptomatic or unstable central nervous system (CNS) metastases that require the use of steroids. Patients who have a stable CNS status for at least 4 weeks before treatment will be allowed to join the study.
• Any evidence of serious or uncontrolled systemic disease, including uncontrolled hypertension and active bleeding diatheses, or active infection including hepatitis B, hepatitis C, syphilis and human immunodeficiency virus (HIV).
• Clinically significant cardiovascular disease, such as mean resting corrected QT interval (QTcF) ≥470 msec (female) or ≥450 msec (male), obtained from 3 ECGs, or any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG or left ventricular ejection fraction (LVEF) ≤ 50%, etc.
• Previous history of interstitial lung disease, drug-induced interstitial lung disease, history of radiation-induced pneumonia requiring hormone therapy, or clinical evidence of active interstitial lung disease.
• Presence of active gastrointestinal disease or other condition that would preclude the absorption, distribution, metabolism, or excretion of study drug.
• Patients currently receiving medications known to be potent inducers, sensitive substrate or potent inhibitor of cytochrome P450 (CYP) 3A4 (e.g. CYP3A4), CYP3A5, CYP2D6 and CYP2C8.
• Patients with a known allergy or delayed hypersensitivity reaction to study drug or its excipient.