D-0316 First Time in Patients Ascending Dose Study

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Phase I Study of D-0316 in Patients With Advanced Non Small Cell Lung Cancer With Mutation of Epidermal Growth Factor Receptor Tyrosine Kinase

Conditions
-----------------
Advanced Non Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: D-0316


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses Histological or cytological confirmation diagnosis of Non Small Cell Lung Cancer (NSCLC). Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib. In addition other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study. Confirmation that the tumour harbours an EGFR T790M mutation. No deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks. Evaluable or measurable disease per RECIST v1.1 Exclusion Criteria: Treatment with an EGFR TKI (erlotinib or gefitinib) within 14 days of the first dose of study treatment. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment. Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daily oral dose of D-0316<br> | Drug: D-0316<br>* 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 defined<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLTs) | Incidence of DLTs | Day 1 - Day 28 | 
| Adverse events | Incidence of AEs | Day 1 - Day 28 | 
| Laboratory results | Incidence of laboratory abnormalities | Day 1 - Day 28 | 
| Vital signs | Incidence of vital sign abnormalities | Day 1 - Day 28 | 
| Electrocardiogram | Incidence of ECG abnormalities | Day 1 - Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic: area under the plasma concentration versus time curve (AUC) | AUC: area under the plasma concentration versus time curve for D-0316 | Day 1 through 6, Cycle Day 1-Day 15 | 
| Pharmacokinetic: maximum plasma drug concentration (Cmax) | Cmax: maximum plasma drug concentration of D-0316 | Day 1 through 6, Cycle Day 1-Day 15 | 
| Pharmacokinetic: Time to reach the Cmax (Tmax) | tmax: Time to reach the Cmax of D-0316 | Day 1 through 6, Cycle Day 1-Day 15 | 
| Pharmacokinetic: Apparent terminal half-life (t1/2) | t1/2: apparent terminal half-life of D-0316 | Day 1 through 6, Cycle Day 1-Day 15 | 
| Antitumor activity | Antitumor activity by evaluation of tumor response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1) | 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 months |