Study of AZD9291 Plus MEDI4736 Versus AZD9291 Monotherapy in NSCLC After Previous EGFR TKI Therapy in T790M Mutation Positive Tumours (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 (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

Study Overview

• Status: Completed
• Conditions: Locally Advanced or Metastatic EGFR T790M+ NSCLC
• Intervention / Treatment: Drug: AZD9291; Drug: MEDI4736

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

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Research Site
  • Daegu, Korea, Republic of, 42601
    • Research Site
  • Incheon, Korea, Republic of, 21565
    • Research Site
  • Jinju-si, Korea, Republic of, 660-702
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 03181
    • Research Site
  • Seoul, Korea, Republic of, 156-707
    • Research Site
  • Ulsan, Korea, Republic of, 44033
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 82445
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI4736 & AZD9291 Combination; 10mg/kg q2w (IV) infusion & once daily tablet 80 mg	Drug: AZD9291; Once daily tablet 80 mg; Drug: MEDI4736; 10mg/kg q2w (IV) infusion
Experimental: AZD9291 Monotherapy; Once daily tablet 80 mg	Drug: AZD9291; Once daily tablet 80 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Baseline up to 3 months after the last dose (up to 24 months).

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Leora Horn, MD, Vanderbilt University, Nashville, USA; Principal Investigator: James CH Yang, MD, National Taiwan University Hospital, Taiwan

Publications and helpful links

Helpful Links

• d5165c00001_CSP
• d5165c00001_SAP

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2015
• Primary Completion (Actual): August 21, 2017
• Study Completion (Actual): June 21, 2023

Study Registration Dates

• First Submitted: May 14, 2015
• First Submitted That Met QC Criteria: May 22, 2015
• First Posted (Estimated): May 27, 2015

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Phase III Open Label Study; AZD9291 plus MEDI4736 versus AZD9291 Monotherapy; NSCLC After Previous EGFR TKI Therapy; T790M Mutation Positive Tumours.
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Durvalumab; Osimertinib
• Other Study ID Numbers: D5165C00001; 2015-001858-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No