Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) MedDRA version: 21.1 Level: PT Classification code 10029519 Term: Non-small cell lung cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MEDI4736
Product Code: MEDI4736
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Other
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed, written and dated informed consent prior to any study specific procedures 2. Male or female aged 18 years or older 3. Patients must have histologically- or cytologically-documented NSCLC who present with locally advanced, unresectable (Stage III) disease 4. Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy. 5. Patients must have not progressed following definitive, platinum-based, concurrent chemoradiation therapy. 6. Provision of an archived tumour tissue block where such samples exist in a quantity sufficient to allow for analysis. 7. Life expectancy =12 weeks 8. World Health Organization (WHO) Performance Status of 0 or 1 9. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. 10. Adequate organ and marrow function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 530 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 470
Exclusion criteria
Exclusion criteria: - Either Previous drug assignment in the present study or Prior randomisation or treatment in a previous durvalumab (MEDI4736) and/or tremelimumab clinical study regardless of treatment arm assignment - Participation in another clinical study with an investigational product during the last 4 weeks. - Concurrent enrolment in another clinical study, - Mixed small cell and non-small cell lung cancer histology - Receipt of sequential chemoradiation therapy for locally advanced NSCLC - Patients with locally advanced NSCLC who have progressed whilst receiving definitive platinum based, concurrent chemoradiation therapy - Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the first dose of study drug - Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required as prophylaxis against or to manage toxicities arising from chemotherapy and/or radiotherapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed. - Prior exposure to any anti-PD-1 or anti-PD-L1 antibody - Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy. - Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included (eg, hearing loss) after consultation with the AstraZeneca/MedImmune medical monitor. - Patients with = grade 2 pneumonitis from prior chemoradiation therapy - Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. - Recent major surgery within 4 weeks - Active or prior documented autoimmune disease within the past 2 years, except for: Vitiligo, Grave's disease, or psoriasis not requiring systemic treatment - Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) - History of primary immunodeficiency - History of allogeneic organ transplant - History of hypersensitivity to MEDI4736 or any excipient - Uncontrolled intercurrent illness - Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study drug. - History of another primary malignancy within 5 years prior to starting study drug, except for adequately treated in situ malignancies such as basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study - Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control - Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of MEDI4736 treatment compared with placebo in terms of OS and PFS;Secondary Objective: - To further assess the efficacy of MEDI4736 compared with placebo in terms of: OS24, ORR, DoR, APF12, APF18, PFS2 and TTDM. - To assess the safety and tolerability profile of MEDI4736 compared with placebo - To assess symptoms and health-related quality of life in patients treated with MEDI4736 compared with placebo;Primary end point(s): Both Progression free survival (PFS) and Overall survival (OS) are co-primary endpoints. OS - Overall Survival is defined as the time from the date of randomization until death due to any cause. PFS - Progression-Free Survival is defined as the time from randomization until the date of objective disease progression or death.;Timepoint(s) of evaluation of this end point: The interim PFS analysis will be done at approx. 27 months, the primary PFS analysis and interim OS analysis will be done at approx. 36 months, the primary OS analysis will be done at approx. 62 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of patients alive at 24 months from randomization (OS24) - Objective response rate (ORR). Defined as the number (%) of patients with at least 1 visit response of CR (Complete response) or PR (Partial response) and will be based on all randomised patients who have measurable disease. ;Timepoint(s) of evaluation of this end point: Analysis of OS24 and ORR will be done at approx. 36 and 62 months. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, European Union, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Philippines, Poland, Singapore, Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed