Patients with unresectable Stage III non-small cell lung cancer (NSCLC), who have not progressed following platinum-based sequential chemoradiation therapy (sCRT) MedDRA version: 20.0 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: Durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DURVALUMAB
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Conce
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Informed consent as detailed in the protocol. - 18 years or older at the time of signing the ICF. - Histologically-or cytologically-documented NSCLC with locally-advanced, unresectable Stage III disease (according to the IASLC Staging Manual Version 8 [IASLC 2016]). Positron emission tomography (PET)/CT, MRI of the brain, and endobronchial ultrasound with biopsy are highly encouraged at diagnosis. - Receipt of sCRT which must have been completed within 28 days prior to first IP dose administration in the study as defined in the protocol. - Patients must not have progressed following platinum-based sCRT, as per Investigator-assessed RECIST 1.1 criteria as defined in the protocol. - Must have a life expectancy of at least 12 weeks at enrolment. - WHO/ECOG PS =2. - Adequate organ and marrow function at enrolment as defined in the protocol. - Body weight >30 kg at enrolment and first IP dose administration. - Male or female. - Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Age-specific requirements are detailed in the protocol. 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 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 105
Exclusion criteria
Exclusion criteria: - Patients with locally-advanced NSCLC whose disease has progressed following platinum-based sCRT. - Patients who have disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumours. - Mixed small-cell lung cancer and NSCLC histology. - History of allogeneic organ transplantation. - Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). Exceptions to this criterion are defined in the protocol. - Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, ILD, serious chronic GI conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent. - History of another primary malignancy except for: -- Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence. -- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. -- Adequately treated carcinoma in situ without evidence of disease. - History of leptomeningeal carcinomatosis. - History of active primary immunodeficiency. - Active infection including tuberculosis, hepatitis B, hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Patients with a past or resolved hepatitis B virus (HBV) infection are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). - Any unresolved toxicity of NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. More details to be found in the protocol. - Known allergy or hypersensitivity to durvalumab (MEDI4736) or any of the IP excipients. - Patients who have received cCRT for locally-advanced NSCLC, or who received sCRT with at least 2 concomitant CRT cycles. Prior surgical resection (ie, Stage I or II) is permitted. - Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. - Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. - Prior exposure to immune-mediated therapy, including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines. - Current or prior use of immunosuppressive medication within 14 days before the first dose of IP. Exceptions to this criterion are detailed in the protocol. - Previous IP assignment in the present study. - Concurrent enrolment in another clinical study, unless it is an observational clinical study or the follow-up period of an interventional study. - Participation in another clinical study with an IP during the 4 weeks prior to the first IP dose administration. - Prior randomisation or treatment in a previous durvalumab (MEDI4736) ± tremelimumab clinical study regardless of tr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To assess the safety and tolerability profile of durvalumab (MEDI4736) as defined by Grade 3 and Grade 4 TRAEs within 6 months from the initiation of durvalumab (MEDI4736) treatment.;Secondary Objective: - To assess the efficacy of durvalumab (MEDI4736) treatment in terms of PFS and OS. - To further assess the efficacy of durvalumab (MEDI4736) treatment in terms of ORR and DoR. - To assess the efficacy of durvalumab (MEDI4736) treatment in terms of lung cancer mortality. - To further assess the safety and tolerability profile of durvalumab (MEDI4736) treatment, including all AEs.;Primary end point(s): Grade 3 or Grade 4 TRAEs;Timepoint(s) of evaluation of this end point: Patients will receive IMP every 4 weeks (q4w) for a maximum of 24 months. Efficacy for all patients will be assessed every 8 weeks (q8w) for the first 12 months and every 12 weeks (q12w) thereafter, until disease progression; plus an additional follow-up scan is performed if clinically feasible. Additional scans can be completed per standard practice post disease progression. Patients who have discontinued treatment will be followed up for 90 days after IP discontinuation, and thereafter followed up with tumour assessments until RECIST 1.1-defined radiological PD plus an additional follow-up scan or until death (whichever comes first). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Median PFS according to RECIST 1.1 as assessed by the Investigator. - PFS12 and PFS24 according to RECIST 1.1 as assessed by the Investigator. - Median OS, OS12, OS24, and OS36. - ORR according to RECIST 1.1 as assessed by the Investigator. - DoR according to RECIST 1.1 as assessed by the Investigator. - Lung cancer mortality. - AEs, SAEs, AESIs, imAEs, physical examinations, vital signs including BP, pulse, ECGs, and laboratory findings including clinical chemistry, haematology and urinalysis.;Timepoint(s) of evaluation of this end point: Patients will receive IMP every 4 weeks (q4w) for a maximum of 24 months. Efficacy for all patients will be assessed every 8 weeks (q8w) for the first 12 months and every 12 weeks (q12w) thereafter, until disease progression; plus an additional follow-up scan is performed if clinically feasible. Additional scans can be completed per standard practice post disease progression. Patients who have discontinued treatment will be followed up for 90 days after IP discontinuation, and thereafter followed up with tumour assessments until RECIST 1.1-defined radiological PD plus an additional follow-up scan or until death (whichever comes first). All patients in the study should be followed up for survival every 12 weeks until death, withdrawal of consent, or the end of the study. | — |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Transparency
AstraZeneca
Outcome results
None listed