Assessing an Oral Janus Kinase Inhibitor, AZD4205, in Combination With Osimertinib in Patients Who Have Advanced Non-small Cell Lung Cancer (JACKPOT1)

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 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.

Study Overview

• Status: Completed
• Conditions: Nonsmall Cell Lung Cancer
• Intervention / Treatment: Drug: AZD4205

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Sydney, Australia, 2066
    • Northern Cancer Institute St Leonards
  • New South Wales
    • Sydney, New South Wales, Australia
      • St George Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Melbourne, Victoria, Australia
      • Peter MacCallum Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: daily dose of AZD4205	Drug: AZD4205; 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.

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

Collaborators and Investigators

• Sponsor: Dizal Pharmaceuticals
• Investigators: Study Director: Pamela Yang, MD, PhD, Dizal (Jiangsu) Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 16, 2018
• Primary Completion (ACTUAL): September 3, 2019
• Study Completion (ACTUAL): January 10, 2020

Study Registration Dates

• First Submitted: January 25, 2018
• First Submitted That Met QC Criteria: February 27, 2018
• First Posted (ACTUAL): March 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 20, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: DZ2017J0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No