Patients with Stage III unresectable Non-small cell lung cancer (NSCLC), who have an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2 and who are treated with radiotherapy but are ineligible for chemotherapy 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: 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]). (a) Imaging to rule out distant metastasis is required. (b) Endobronchial ultrasound with biopsy is encouraged in patients with suspected lymph node involvement. - Deemed ineligible for chemotherapy per Investigator assessment (eg, comorbidities, poor PS, etc). - Receipt of radiation therapy that was completed within 42 days prior to first IP dose administration in the study. - Patients must have received a total dose of radiation of 40 to 66 Gy (standard or hypofractionated BED). Further details are provided in the protocol. - Patients must not have progressed following radiation therapy, as per Investigator assessed RECIST 1.1 criteria as defined in the protocol. - WHO/ECOG PS of = 2. - No prior exposure to immune-mediated therapy including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, and antiprogrammed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines. - Adequate organ and marrow function as defined in the protocol. - Must have a life expectancy of at least 12 weeks. - Body weight > 30 kg at enrollment and first IP dose administration - Male or female 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: - Patients with locally-advanced NSCLC whose disease has progressed following radiation therapy. - Mixed small cell lung cancer and NSCLC histology. - History of allogeneic organ transplantation. - Active or prior documented autoimmune or inflammatory disorders as defined in the protocol. - Uncontrolled intercurrent illness as defined in the protocol. - History of another primary malignancy except for (1) Malignancy treated with curative intent and with no known active disease = 5 years before the first dose of durvalumab and of low potential risk for recurrence (2) Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease (3) 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, or human immunodeficiency virus (HIV; positive HIV 1/2 antibodies). - Any unresolved toxicity NCI CTCAE Grade = 2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criteria -Patients with Grade = 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. -Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. - Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients Prior/concomitant therapy - Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. - Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab. - Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. Please refer to protocol for exceptions. - Participation in another clinical study with an IP administered in the last 4 weeks - Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study - Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment Please refer to the protocol pages 38-39 for further criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs within 6 months from the initiation of durvalumab treatment;Secondary Objective: -To assess the efficacy of durvalumab treatment in terms of PFS and OS -To further assess the efficacy of durvalumab treatment in terms of ORR and DoR -To assess the efficacy of durvalumab treatment in terms of lung cancer mortality -To further assess the safety and tolerability profile of durvalumab treatment, including all AEs;Primary end point(s): Grade 3 and Grade 4 PRAEs;Timepoint(s) of evaluation of this end point: Within 6 months after the initiation of durvalumab treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Median PFS according to RECIST 1.1 as assessed by the Investigator PFS6 and PFS12 according to RECIST 1.1 as assessed by the Investigator Median OS and OS12 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, hematology, and urinalysis;Timepoint(s) of evaluation of this end point: Median PFS; proportion of patients progression-free at 6 and 12 months. Median OS; proportion of patients alive at 12 months. | — |
Countries
France, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Transparency
AstraZeneca
Outcome results
None listed