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

NCT02454933 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: D5165C000012015-001858-15
• Study Type: interventional
• Target: 29
• Locations: 3 countries
• Sites: 13

Brief 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

Conditions

Locally Advanced or Metastatic EGFR T790M+ NSCLC

Keywords

Phase III Open Label Study; AZD9291 plus MEDI4736 versus AZD9291 Monotherapy; NSCLC After Previous EGFR TKI Therapy; T790M Mutation Positive Tumours.

Outcome Measures

Primary Outcomes (1)

• 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 primary analysis data cut-off (up to 24 months).

Study Arms (2)

MEDI4736 & AZD9291 Combination

EXPERIMENTAL

10mg/kg q2w (IV) infusion \& once daily tablet 80 mg

Drug: AZD9291; Drug: MEDI4736

AZD9291 Monotherapy

EXPERIMENTAL

Once daily tablet 80 mg

Drug: AZD9291

Interventions

AZD9291 DRUG

Once daily tablet 80 mg

AZD9291 Monotherapy; MEDI4736 & AZD9291 Combination

MEDI4736 DRUG

10mg/kg q2w (IV) infusion

MEDI4736 & AZD9291 Combination

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (13)

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Busan, 47392, South Korea

Location

Research Site

Daegu, 42601, South Korea

Location

Research Site

Incheon, 21565, South Korea

Location

Research Site

Jinju, 660-702, South Korea

Location

Research Site

Seongnam-si, 13620, South Korea

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 03181, South Korea

Location

Research Site

Seoul, 156-707, South Korea

Location

Research Site

Ulsan, 44033, South Korea

Location

Research Site

Kaohsiung City, 82445, Taiwan

Location

Research Site

Taichung, 40705, Taiwan

Location

Research Site

Taipei, 10002, Taiwan

Location

Related Links

• d5165c00001\_CSP
• d5165c00001\_SAP
• CSR Synopsis\_Redacted
• CSR synopsis addendum

MeSH Terms

Interventions

osimertinib; durvalumab

Limitations and Caveats

Subject enrolment was terminated early on 29 September 2015 after higher than anticipated incidence of interstitial lung disease-like events in subjects receiving osimertinib + durvalumab in a separate Phase Ib open-label study D5160C00006 (TATTON).

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

+1 302 885 1180

Study Officials

• Leora Horn, MD

  Vanderbilt University, Nashville, USA

  PRINCIPAL INVESTIGATOR

• James CH Yang, MD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: May 27, 2015
• Study Start: July 15, 2015
• Primary Completion: August 21, 2017
• Study Completion: June 21, 2023
• Last Updated: September 19, 2024
• Results First Posted: August 10, 2018

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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
• 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

Locations

TW (3); KR (9); CA (1)