AZD9291 in Combination With Ascending Doses of Novel Therapeutics

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

Conditions

• Advanced Non Small Cell Lung Cancer

Interventions

DRUG

Part A - AZD9291 in combination with AZD6094

Part A - AZD9291 and AZD6094 administered in different doses to investigate the safety and tolerability of this combination and define the combination dose for further clinical evaluation in Part B.

DRUG

Part A - AZD9291 in combination with continuous selumetinib (Asian subjects)

Part A - AZD9291 and selumetinib (continuous treatment) administered in different doses to investigate the safety and tolerability of this combination in Asian subjects and to define the combination dose for further clinical evaluation in Part B.

DRUG

Part A - AZD9291 in combination with continuous selumetinib (non-Asian subjects)

Part A - AZD9291 and selumetinib (continuous treatment) administered in different doses to investigate the safety and tolerability of this combination in non-Asian subjects and to define the combination dose for further clinical evaluation in Part B.

DRUG

Part A - AZD9291 in combination with intermittent selumetinib

Part A - AZD9291 and selumetinib (intermittent treatment) administered in different doses to investigate the safety and tolerability of this combination and to define the combination dose for further clinical evaluation in Part B.

DRUG

Part A - AZD9291 in combination with MEDI4736

Part A - AZD9291 and MEDI4736 administered in different doses to investigate the safety and tolerability of this combination and to define the combination dose for further clinical evaluation in Part B. Note: 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.

DRUG

Part B - AZD9291 in combination with AZD6094

Part B - AZD9291 and AZD6094 administered in the dose identified in Part A (AZD9291 80mg OD + AZD6094 600mg OD) to further investigate the safety and tolerability of this combination.

DRUG

Part B - AZD9291 in combination with selumetinib

Part B - AZD9291 and selumetinib administered in the dose identified in Part A (AZD9291 80mg OD + selumetinib 75 mg BD intermittent \[4 days on/3 days off\]) to further investigate the safety and tolerability of this combination.

DRUG

Part B - AZD9291 in combination with MEDI4736

Part B - AZD9291 and MEDI4736 administered in the dose identified in Part A to further investigate the safety and tolerability of this combination. Note: 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.

DRUG

Part C - AZD6094 monotherapy (Japan only)

Part C - AZD6094 monotherapy to assess the safety, tolerability and pharmacokinetics of the monotherapy of AZD6094 in Japanese patients with advanced NSCLC.

DRUG

Part C - AZD9291 in combination with AZD6094 (Japan only)

Part C combination cohort - AZD9291 80mg OD administered in combination with AZD6094 400mg OD (AZD6094 dose in which DLTs have not been identified in the Japanese monotherapy cohort) in order to confirm the safety, tolerability, pharmacokinetics and preliminary anti-tumor activities of this combination in Japanese subjects. The 400mg OD dosing schedule will be initiated in the first cohort. The dose may be subsequently reduced in further cohorts in response to emerging safety, or PK findings or other reasons identified in the savolitinib programme.

DRUG

Part D - AZD9291 in combination with AZD6094

Part D - AZD9291 80mg OD administered in combination with AZD6094 300mg OD to further evaluate the safety, tolerability, pharmacokinetics and antitumor activity in terms of ORR and PFS in patients with locally advanced or metastatic cMET positive EGFRm+ and T790M-negative NSCLC, following progression on EGFR-TKI treatment. The choice of AZD6094 dose of 300 mg is based on results from preclinical and clinical studies. Clinical testing of the 300 mg OD dose will enable better assessment of impact of lower AZD6094 exposure on overall tolerability and hepatotoxicity risk as well as exploration of the efficacy and overall safety profiles with a dose meaningfully lower than the current dose of 600 mg OD.

Sponsors & Collaborators

• AstraZeneca

  lead INDUSTRY

Principal Investigators

• Pasi A Jänne, MD, PhD · Dana-Faber Cancer Institute

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

130 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-08-05

Primary Completion

2020-03-04

Completion

2026-12-31

Countries

• United States
• Canada
• Japan
• Poland
• Russia
• South Korea
• Taiwan
• Ukraine

Study Locations