This is a phase 1 open label multicentre study of D-0316 administered orally in patients with advanced NSCLC who have progressed following prior therapy with an EGFR-TKI (Epidermal Growth Factor Receptor tyrosine kinase inhibitor agent). This is the first time this drug has ever been tested in patients, and so it will help to understand safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of ascending doses of D-0316.
Name: D-0316
Description: If initial dosing of D-0316 is tolerated then subsequent cohorts will test increasing doses until a maximum tolerated dose or maximum feasible dose is definedType: DrugDaily oral dose of D-0316
Description: Incidence of DLTs
Measure: Dose Limiting Toxicities (DLTs) Time: Day 1 - Day 28Description: Incidence of AEs
Measure: Adverse events Time: Day 1 - Day 28Description: Incidence of laboratory abnormalities
Measure: Laboratory results Time: Day 1 - Day 28Description: Incidence of vital sign abnormalities
Measure: Vital signs Time: Day 1 - Day 28Description: Incidence of ECG abnormalities
Measure: Electrocardiogram Time: Day 1 - Day 28Description: AUC: area under the plasma concentration versus time curve for D-0316
Measure: Pharmacokinetic: area under the plasma concentration versus time curve (AUC) Time: Day 1 through 6, Cycle Day 1-Day 15Description: Cmax: maximum plasma drug concentration of D-0316
Measure: Pharmacokinetic: maximum plasma drug concentration (Cmax) Time: Day 1 through 6, Cycle Day 1-Day 15Description: tmax: Time to reach the Cmax of D-0316
Measure: Pharmacokinetic: Time to reach the Cmax (Tmax) Time: Day 1 through 6, Cycle Day 1-Day 15Description: t1/2: apparent terminal half-life of D-0316
Measure: Pharmacokinetic: Apparent terminal half-life (t1/2) Time: Day 1 through 6, Cycle Day 1-Day 15Description: Antitumor activity by evaluation of tumor response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Measure: Antitumor activity Time: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 monthsSingle Group Assignment
There is one SNP
- Confirmation that the tumour harbours an EGFR T790M mutation. --- T790M ---