AZD9291 in Combination With Ascending Doses of Novel Therapeutics

Official Title

A Multi-arm, Phase Ib, Open-Label, Multicentre Study to Assess the Safety,Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Combination With Ascending Doses of Novel Therapeutics in Patients With EGFRm+ Advanced NSCLC Who Have Progressed Following Therapy With an EGFR TKI (TATTON).

Summary:

The purpose of this study is to determine the safety, tolerability and preliminary anti-tumour activity of AZD9291 when given together with AZD6094 or selumetinib in patients with EGFR mutation positive advanced lung cancer.

Trial Description

Primary Outcome:

  • Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and Tolerability of AZD9291 when given in combination with AZD6094 or selumetinib
  • Number of participants with Adverse Events as a measure of Safety and Tolerability of AZD9291 when given in combination with AZD6094 or selumetinib
Secondary Outcome:
  • Cmax after single dosing
  • Tmax after single dosing
  • AUC after single dosing
  • AUC0-t after single dosing
  • AUC0-24 after single dosing
  • Terminal half life after single dosing
  • CL/f after single dosing
  • Volume of distribution after single dosing
  • Cssmax after multiple dosing
  • Tssmax after multiple dosing
  • Cssmin after multiple dosing
  • AUCss after multiple dosing
  • CLss/f after multiple dosing
  • Rac after multiple dosing
  • Time dependency of PK after multiple dosing
  • Objective response rate
  • Disease control rate
  • Duration of response
  • Percentage change in tumour size
  • Progression free survival
  • Overall survival
This is a Phase Ib, open-label, multicentre study of AZD9291 administered orally in combination with novel therapeutics (AZD6094 or selumetinib (AZD6244, ARRY142886)) to patients with EGFRm+ advanced NSCLC. The study has been designed to allow an investigation of the optimal combination dose and schedule whilst ensuring the safety of patients with intensive safety monitoring. There are three main parts to this study; Part A, Combination dose finding and Parts B and D, Dose expansion. Part C, AZD6094 dose finding sub-study in advanced solid tumour patients is ongoing in Japan. AZD9291 (osimertinib) is a potent irreversible inhibitor of both the single epidermal growth factor receptor sensitising mutation positive (EGFRm+) (tyrosine kinase inhibitor [TKI] sensitivity-conferring mutation) and dual EGFRm+/T790M+ (TKI resistance-conferring mutation) receptor forms of EGFR. AZD9291 therefore has the potential to provide clinical benefit to patients with advanced non-small cell lung cancer (NSCLC) harbouring both the single sensitivity mutations and the resistance mutation following prior therapy with an EGFR TKI. AZD9291 (osimertinib) was awarded FDA accelerated approval in November 2015, followed by conditional approval in the EU, full approval in Japan and additional markets in 2016, for the treatment of patients with EGFR T790M+ NSCLC who have progressed on or after EGFR TKI therapy. Enrolment into the patient cohort that evaluated AZD9291 treatment in combination with MEDI4736 as 1st line treatment has been terminated due to an increased incidence of ILD-like events (interstitial lung disease/pneumonitis), and is no longer being evaluated in this study.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society