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
Active, not recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| AZD9291 | AZD9291 Monotherapy | |
| MEDI4736 | MEDI4736 & AZD9291 Combination |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| MEDI4736 & AZD9291 Combination | Experimental | 10mg/kg q2w (IV) infusion & once daily tablet 80 mg |
|
| AZD9291 Monotherapy | Experimental | Once daily tablet 80 mg |
|
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
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| 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 3 months after the last dose (up to 24 months). |
| Safety Issue: | |
| Description: | 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. |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | AstraZeneca |
July 23, 2021
