Locally Advanced or Metastatic EGFR T790M+ NSCLCPhase 3CAURALNCT02454933
Study of AZD9291 Plus MEDI4736 Versus AZD9291 Monotherapy in NSCLC After Previous EGFR TKI Therapy in T790M Mutation Positive Tumours
A Phase 3 study testing AZD9291 and MEDI4736 in people with Locally Advanced or Metastatic EGFR T790M+ NSCLC, run by AstraZeneca at 13 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Locally Advanced or Metastatic EGFR T790M+ NSCLC
- What is being tested?
- AZD9291 and MEDI4736
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 13 sitesin 3 countries
- Study dates
- 15 Jul 2015to 21 Jun 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
South Korea9 sites
Research Site
Busan, 47392
Research Site
Daegu, 42601
Research Site
Incheon, 21565
Research Site
Jinju, 660-702
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 03181
Research Site
Seoul, 156-707
Research Site
Ulsan, 44033
Taiwan3 sites
Research Site
Kaohsiung City, 82445
Research Site
Taichung, 40705
Research Site
Taipei, 10002
About this study
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)
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
Read the detailed 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 investigate the safety and tolerability profile of AZD9291 in combination with MEDI4736.
350 patients were originally planned to be evaluated across the two below populations. The recruitment was stopped due to new information on safety of the combination, received from another trial in similar patient population
- 2nd line: patients who have progressed following an approved first-line EGFR-TKI treatment but who have not received further treatment.
- 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.
- Being tested
- AZD9291, MEDI4736
- Keywords
- Phase III Open Label Study; AZD9291 plus MEDI4736 versus AZD9291 Monotherapy; NSCLC After Previous EGFR TKI Therapy; T790M Mutation Positive Tumours.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9291Drug
Once daily tablet 80 mg
MEDI4736Drug
10mg/kg q2w (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| MEDI4736 & AZD9291 Combination | Experimental | 10mg/kg q2w (IV) infusion \& once daily tablet 80 mg Receives: Drug: AZD9291; Drug: MEDI4736 |
| AZD9291 Monotherapy | Experimental | Once daily tablet 80 mg Receives: Drug: AZD9291 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Adverse Events (AEs) as a Measure of the Safety and Tolerability of Osimertinib in Combination With Durvalumab
As a measure of the safety and tolerability of osimertinib in combination with durvalumab the number of subjects who experienced any treatment emergent AE (TEAE), any causally related AE, any serious AE (SAE), and any causally related SAE are presented.
Measured: From Baseline up to primary analysis data cut-off (up to 24 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2015 (estimated)
- Study start15 Jul 2015
- Primary completion21 Aug 2017
- Study completion21 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Locally Advanced or Metastatic EGFR T790M+ NSCLCStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Leora Horn, MD, Principal investigator, Vanderbilt University, Nashville, USAJames CH Yang, MD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02454933
- Sponsor's protocol ID
- D5165C00001
- Other IDs
- 2015-001858-15, 2015
- Acronym
- CAURAL
- Status last verified
- Sep 2024
- First submitted
- 14 May 2015
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02454933
- Acronym / sponsor ID
- CAURAL / D5165C00001
- Keywords
- Phase III Open Label Study; AZD9291 plus MEDI4736 versus AZD9291 Monotherapy; NSCLC After Previous EGFR TKI Therapy; T790M Mutation Positive Tumours.
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 15 Jul 2015 (actual)
- Primary completion
- 21 Aug 2017 (actual)
- Study completion
- 21 Jun 2023 (actual)
- First posted
- 27 May 2015 (estimated)
- Results
- Posted 10 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed 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 investigate the safety and tolerability profile of AZD9291 in combination with MEDI4736.
350 patients were originally planned to be evaluated across the two below populations. The recruitment was stopped due to new information on safety of the combination, received from another trial in similar patient population
- 2nd line: patients who have progressed following an approved first-line EGFR-TKI treatment but who have not received further treatment.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MEDI4736 & AZD9291 Combination | Experimental | Drug: AZD9291, Drug: MEDI473610mg/kg q2w (IV) infusion \& once daily tablet 80 mg |
| AZD9291 Monotherapy | Experimental | Drug: AZD9291Once daily tablet 80 mg |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD9291Once daily tablet 80 mg | Drug | AZD9291 Monotherapy, MEDI4736 & AZD9291 Combination |
| MEDI473610mg/kg q2w (IV) infusion | Drug | MEDI4736 & AZD9291 Combination |
Primary outcome
Number of Subjects With Adverse Events (AEs) as a Measure of the Safety and Tolerability of Osimertinib in Combination With Durvalumab
Time frame: From Baseline up to primary analysis data cut-off (up to 24 months).
As a measure of the safety and tolerability of osimertinib in combination with durvalumab the number of subjects who experienced any treatment emergent AE (TEAE), any causally related AE, any serious AE (SAE), and any causally related SAE are presented.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- d5165c00001\_CSPLink provided by the sponsor.
- d5165c00001\_SAPLink provided by the sponsor.
- CSR Synopsis\_RedactedLink provided by the sponsor.
- CSR synopsis addendumLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Related trials for Locally Advanced or Metastatic EGFR T790M+ NSCLC
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A Study of BH-30643 in Subjects With Locally Advanced or Metastatic NSCLC Harboring EGFR and/or HER2 Mutations
NSCLC (Advanced Non-small Cell Lung Cancer)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leora Horn, MD principal investigator
Vanderbilt University, Nashville, USA
James CH Yang, MD principal investigator
National Taiwan University Hospital
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AZD9291 and MEDI4736 in people with Locally Advanced or Metastatic EGFR T790M+ NSCLC, run by AstraZeneca at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in South Korea, Taiwan, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Adverse Events (AEs) as a Measure of the Safety and Tolerability of Osimertinib in Combination With Durvalumab (time frame: From Baseline up to primary analysis data cut-off (up to 24 months).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.