Study identifier:D5160C00006
ClinicalTrials.gov identifier:NCT02143466
EudraCT identifier:2016-004752-29
CTIS identifier:N/A
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).
Advanced Non Small Cell Lung Cancer
Phase 1
No
Part A - AZD9291 in combination with AZD6094, Part A - AZD9291 in combination with continuous selumetinib (Asian subjects), Part A - AZD9291 in combination with continuous selumetinib (non-Asian subjects), Part A - AZD9291 in combination with intermittent selumetinib, Part A - AZD9291 in combination with MEDI4736, Part B - AZD9291 in combination with AZD6094, Part B - AZD9291 in combination with selumetinib, Part B - AZD9291 in combination with MEDI4736, Part C - AZD6094 monotherapy (Japan only), Part C - AZD9291 in combination with AZD6094 (Japan only), Part D - AZD9291 in combination with AZD6094
All
344
Interventional
18 Years - 130 Years
Allocation: Non-randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Verified 01 Jun 2025 by AstraZeneca
AstraZeneca
-
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
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. .
Location
Location
Taipei, Taiwan, Province of China, 10002
Location
Kashiwa, Japan, 227-8577
Location
Chuo-ku, Japan, 104-0045
Location
Nagoya-shi, Japan, 460-0001
Location
Seoul, Republic of Korea, 6351
Location
Seoul, Republic of Korea, 05505
Location
New York, NY, United States, 10065
Location
Atlanta, GA, United States, 30329
Arms | Assigned Interventions |
---|---|
Experimental: AZD6094 AZD9291 in combination with AZD6094 | 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. Other Name: Osimertinib & Savolitinib/Volitinib 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. Other Name: Osimertinib & Savolitinib/Volitinib 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. Other Name: Osimertinib & Savolitinib/Volitinib 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. Other Name: Osimertinib & Savolitinib/Volitinib |
Experimental: Selumetinib AZD9291 in combination with selumetinib | 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. Other Name: Osimertinib & ARRY-142886 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. Other Name: Osimertinib & ARRY-142886 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. Other Name: Osimertinib & ARRY-142886 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. Other Name: Osimertinib & ARRY-142886 |
Experimental: MEDI4736 AZD9291 in combination with MEDI4736. 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 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. Other Name: Osimertinib & Durvalumab 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. Other Name: Osimertinib & Durvalumab |
Experimental: AZD6094 (monotherapy) AZD6094 in monotherapy (for Japan only) | 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. Other Name: Savolitinib/Volitinib |
This information is not intended to replace the informed medical advice or medical treatments of a healthcare professional. Only a physician can determine if a specific medicine is the correct treatment for a particular patient. If you have questions regarding any information contained in this site, you must consult a suitably qualified healthcare professional. Before prescribing any AstraZeneca products, Healthcare Professionals should view their country specific information.