Overview

This trial is active, not recruiting.

Condition locally advanced or metastatic egfr t790m+ nsclc
Treatments azd9291, medi4736
Phase phase 3
Targets EGFR, PD-1
Sponsor AstraZeneca
Start date July 2015
End date August 2018
Trial size 29 participants
Trial identifier NCT02454933, D5165C00001

Summary

A Phase III, Multi-Centre, Open Label, Randomized Study to Assess the Efficacy and Safety of AZD9291 in Combination with MEDI4736 versus AZD9291 Monotherapy in patients with Locally Advanced or Metastatic Epidermal Growth Factor Receptor T790M mutation-positive Non-Small Cell Lung Cancer who have received Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
10mg/kg q2w (IV) infusion & once daily tablet 80 mg
azd9291
Once daily tablet 80 mg
medi4736
10mg/kg q2w (IV) infusion
(Experimental)
Once daily tablet 80 mg
azd9291
Once daily tablet 80 mg

Primary Outcomes

Measure
PFS according to RECIST 1.1
time frame: At baseline and every 8 weeks from time of first dose and every 12 weeks after 48 weeks from time of first dose. Participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 16 months

Secondary Outcomes

Measure
ORR according to RECIST 1.1
time frame: At baseline and every 8 weeks from time of first dose and every 12 weeks after 48 weeks from time of first dose. Participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 16 months
DoR according to RECIST 1.1
time frame: At baseline and every 8 weeks from time of first dose and every 12 weeks after 48 weeks from time of first dose. Participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 16 months
DCR according to RECIST 1.1
time frame: At baseline and every 8 weeks from time of first dose and every 12 weeks after 48 weeks from time of first dose. Participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 16 months
Overall Survival
time frame: From first dose to end of study or date of death from any cause, whichever comes first, assessed every 8 weeks up to approximately 60 months
Tumour shrinkage according to RECIST 1.1
time frame: At baseline and every 8 weeks from time of first dose and every 12 weeks after 48 weeks from time of first dose. Participants will be followed by CT/MRI scans for RECIST 1.1 until date of progression, for an average of approximately 16 months
Number of subjects with Adverse Events as a measure of safety and tolerability of AZD9291 as a single agent and in combination with MEDI4736
time frame: Adverse events will be collected from baseline until 3 months after the last dose, expected average 16 months
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30) & EORTC QLQ - Lung Cancer 13 items (EORTC QLQ LC13) measuring patients general cancer symptoms and functioning
time frame: From first dose, every week for the first 18 weeks and then every 3 weeks thereafter for up to approximately 60 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Aged at least 18 years. Japan patients aged at least 20 years. - Locally advanced/metastatic NSCLC, not amenable to curative surgery or radiotherapy - Confirmation from a previous archival sample that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity - Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI. Additional other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study. - Patients must have central lab confirmation of tumour T790M status from a biopsy taken after disease progression on the most recent treatment regimen. Only patients with T790M+ will be included in the study - At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥ 15mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements - World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks - Females of child-bearing potential using contraception; negative pregnancy test Exclusion Criteria: - Treatment with an EGFR-TKI within 5x half-life of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; current treatment with potent inhibitors/inducers of cytochrome P450 3A4 (CYP3A4); previous treatment with AZD9291 (or other agents specifically targeted against EGFR T790M mutation positive NSCLC); Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months of starting 1st EGFR TKI treatment; prior exposure to immune-mediated therapy including, but not limited to, other anti cytotoxic T-lymphocyte-associated antigen 4 (anti CTLA-4), anti- programmed cell death 1 (anti-PD-1), anti- programmed cell death ligand 1 (anti-PD-L1), and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks; major surgery within 4 weeks; - Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 (excluding intranasal, inhaled, topical steroids, or local steroid injections) - Unresolved toxicities from prior therapy - History of active primary immunodeficiency - Unstable brain metastases or spinal cord compression - Severe/uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, bleeding diatheses or infection - Cardiac disease - Ophthalmological conditions - Refractory nausea/vomiting, chronic gastrointestinal diseases or bowel resection - Past history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. - History of another primary malignancy - Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment - History of organ transplant that requires use of immunosuppressive medications - Known history of tuberculosis - Receipt of live, attenuated vaccine within 30 days prior to the first dose of MEDI4736 - Inadequate bone marrow reserve or organ function

Additional Information

Official title A Phase III, Multi-Centre, Open Label, Randomized Study to Assess the Efficacy and Safety of AZD9291 in Combination With MEDI4736 Versus AZD9291 Monotherapy in Patients With Locally Advanced or Metastatic Epidermal Growth Factor Receptor T790M Mutation-positive Non-Small Cell Lung Cancer Who Have Received Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy (CAURAL)
Principal investigator Leora Horn, MD
Description This a phase III, Multi Centre, Open Label, Randomized, Study to Assess the Efficacy and Safety of AZD9291 (80 mg, orally, once daily) in Combination with MEDI4736 (10 mg/kg (IV) infusion q2w) versus AZD9291 Monotherapy (80 mg, orally, once daily) in patients with a confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) T790M mutation positive NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent. The randomization will be stratified by previous lines of treatment (2nd or 3rd+) and ethnicity (Asian or Non-Asian). A mandatory biopsy will be needed for central testing of T790M mutation status following confirmed disease progression on the most recent treatment regimen. The primary objective of the study is to assess the efficacy of AZD9291 in combination with MEDI4736 versus AZD9291 monotherapy by assessment of Progression Free Survival (PFS) by investigators according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Approximately 350 patients will be evaluated and will consist of 2 populations: 1. 2nd line: patients who have progressed following an approved first-line EGFR-TKI treatment but who have not received further treatment. 2. 3rd line or higher: patients who have progressed following prior therapy with an approved EGFR-TKI and an additional anti-cancer treatment. Patients may have also received additional lines of treatment.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.