Assessing an Oral Janus Kinase Inhibitor, AZD4205, in Combination With Osimertinib in Patients Who Have Advanced Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
This study will treat patients with advanced NSCLC who have progressed following prior therapy. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment. It will also measure the levels of drug in the body and preliminarily assess its anti-cancer activity as monotherapy and in combination with Osimertinib.

Detailed Description
-----------------
A phase I/II, open-label, multicentre study to investigate the safety, tolerability, pharmacokinetics and anti-tumour activity of AZD4205 as monotherapy or in combination with Osimertinib in patients with EGFR mutant advanced stage non-small cell lung cancer (NSCLC). This study includes dose escalation part and dose expansion part.

Official Title
-----------------
A Phase I/II, Open-Label, Multicentre Study to Investigate the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AZD4205 as Monotherapy or in Combination With Osimertinib in Patients With EGFR Mutant Advanced Stage Non-Small Cell Lung Cancer (NSCLC)

Conditions
-----------------
Nonsmall Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: AZD4205


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obtained written informed consent Patients must have histological or cytological confirmation of activating EGFR mutation positive NSCLC and have failed prior EGFR TKIs treatment. Patients must exhibit Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Adequate bone marrow reserve and organ system functions Exclusion Criteria: Any unsolved toxicity > CTCAE grade 1 from previous anti-cancer therapy (except alopecia) Active viral or bacterial infections; Active or latent tuberculosis; History of interstitial lung disease (ILD) History of heart failure or QT interval prolongation Immunodeficiency diseases; Active CNS metastases Treatment with an EGFR TKI (e.g., erlotinib or gefitinib) within 8 days or approximately 5 x half-life, whichever is longer, of the first dose of study treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 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
Interventional Model Description: dose escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: daily dose of AZD4205<br>daily dose of AZD4205 | Drug: AZD4205<br>* Daily dose of AZD4205, followed by daily dose of AZD4205 and Osimertinib 80 mg. Starting dose of AZD4205 at 75 mg, administered once daily. If tolerated, subsequent cohorts will test increasing doses of AZD4205, and in combination with Osimertinib 80 mg.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of AZD4205 | Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v4.0 | 21 days after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (by investigator assessment) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy. | RECIST tumour assessments every 6 weeks from enrollment until study completion, an average of 1 year | 
| Peak Plasma Concentration (Cmax) of AZD4205 | Peak Plasma Concentration (Cmax) of AZD4205 | 1,8,15 days after first dose | 
| Area under the plasma concentration versus time curve (AUC) of AZD4205 | Area under the plasma concentration versus time curve (AUC) of AZD4205 | 1,8,15 days after first dose |