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

Phase 1

Completed

• Conditions: Nonsmall Cell Lung Cancer
• Interventions: Drug: AZD4205

• Registration Number: NCT03450330
• Lead Sponsor: Dizal Pharmaceuticals

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.

Study Timeline

• Study First Submitted: 2018-01-25
• Study First Submitted QC: 2018-02-27
• Study First Posted: 2018-03-01
• Study Start: 2018-04-16
• Primary Completion: 2019-09-03
• Status Verified: 2019-11
• Study Completion: 2020-01-10
• Last Update Submitted: 2020-08-20
• Last Update Posted: 2020-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

1. Obtained written informed consent
2. Patients must have histological or cytological confirmation of activating EGFR mutation positive NSCLC and have failed prior EGFR TKIs treatment.
3. Patients must exhibit Eastern Cooperative Oncology Group (ECOG) performance status 0-1
4. Adequate bone marrow reserve and organ system functions

Exclusion Criteria

1. Any unsolved toxicity > CTCAE grade 1 from previous anti-cancer therapy (except alopecia)
2. Active viral or bacterial infections;
3. Active or latent tuberculosis;
4. History of interstitial lung disease (ILD)
5. History of heart failure or QT interval prolongation
6. Immunodeficiency diseases;
7. Active CNS metastases
8. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
daily dose of AZD4205	AZD4205	daily dose of AZD4205

Primary Outcome Measures

Name	Time	Method
safety and tolerability of AZD4205	21 days after the first dose	Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v4.0

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	RECIST tumour assessments every 6 weeks from enrollment until study completion, an average of 1 year	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.
Peak Plasma Concentration (Cmax) of AZD4205	1,8,15 days after first dose	Peak Plasma Concentration (Cmax) of AZD4205
Area under the plasma concentration versus time curve (AUC) of AZD4205	1,8,15 days after first dose	Area under the plasma concentration versus time curve (AUC) of AZD4205

Trial Locations

Locations (4)

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

Northern Cancer Institute St Leonards; 🇦🇺 Sydney, Australia

Austin Hospital; 🇦🇺 Heidelberg, Victoria, Australia

St George Hospital; 🇦🇺 Sydney, New South Wales, Australia