Non-small cell lung cancer stage IV MedDRA version: 20.0 Level: HLT Classification code 10029664 Term: Non-small cell neoplasms malignant of the respiratory tract cell type specified System Organ Class: 100000004864
Conditions
Interventions
Product Name: Durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IMFINZI
Other descriptive name: DURVALUMAB
Concentration unit: mg/ml mil
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent Form 2. Age =18 years at time of study entry 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 4. Histologically or cytologically confirmed, stage IV NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system). 5. Indication for standard-of-care second line platinum-based chemotherapy, using cisplatin or carboplatin in combination with pemetrexed, paclitaxel, nab-paclitaxel, vinorelbine or gemcitabine 6. Life expectancy of > 12 weeks 7. Body weight > 30 kg 8. First-line mono-immunotherapy with checkpoint inhibitors (anti-PD1/PD-L1) with a best response of stable disease (SD) or better 9. Documented tumor PD-L1 expression status of =50%. Any existing data can be used. 10. First-line progression-free survival of at least 12 weeks after at least two reassessments after initiation of first-line treatment. 11. Patients who have received prior neo-adjuvant or adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from initiation of first-line immunotherapy since the last adjuvant chemotherapy or chemoradiotherapy cycle. 12. Patients with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria: - No ongoing requirement for corticosteroids as therapy for CNS disease - No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to enrolment - No evidence of interim progression between the completion of CNS-directed therapy and the screening - Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord) 13. No known sensitizing mutation in the EGFR gene or evidence of an ALK fusion oncogene. 14. Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation. 15. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 3 days prior to enrolment: a. ANC 1500 cells/µL without granulocyte colony-stimulating factor support b. Lymphocyte count = 500/µL c. Platelet count = 100,000/µL without transfusion d. Hemoglobin = 9.0 g/dL. Patients may be transfused to meet this criterion. Transfusions are allowed throughout the study. e. Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. f. AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN g. Measured creatinine clearance (CL) >60 mL/min or calculated creatinine clearance CL>60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance 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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
Exclusion criteria: 1. Use of immunosuppressive medication (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization. 2. Prior treatment with other immune-modulating agents (other than anti-PD-1/PD-L1) 3. Treatment with systemic immunostimulatory agents (including but not limited to IFNs, IL-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to randomization. Prior treatment with cancer vaccines is allowed. 4. Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site) 5. Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study 6. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to randomization 7. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy (including second line platinum-based chemotherapy) with the exception of alopecia, vitiligo, 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 Chair. - Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Chair. 8. Any toxicity that led to permanent discontinuation of prior immunotherapy. 9. AE = grade 4 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy. 10. Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non–cancerrelated conditions (e.g., hormone replacement therapy) is acceptable. 11. History of allogenic organ transplantation. 12. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 13. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., 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.]). The following are exceptions to this criterion: - vitiligo or alopecia - hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement - Any chronic skin condition that does not require systemic therapy - without active disease in the last 5 years may be included but only after consultation with the Study Chair - celiac disease controlled by diet alone 14. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, 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 15. History of another
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary endpoint is progression-free survival 1 (PFS1) using Investigator assessments according to RECIST 1.1. PFS1 is defined as the time from randomization to disease progression and will be primarily used for the formal hypothesis test.;Secondary Objective: The secondary objectives are as follows: - Progression-free survival after initiation of second-line therapy (PFS2) - Overall survival after initiation of second-line therapy (OS) - Objective response rate (ORR) - best overall response during second line treatment - Subgroup analysis: Objective response rate (best overall response) after randomization - Duration of response (DoR) - TFST (Time to first subsequent treatment): Time from initiation of second line treatment to initiation of third line treatment. - Tolerability and adverse events - Quality of life - Biomarkers;Primary end point(s): The primary endpoint is progression-free survival 1 (PFS1) using Investigator assessments according to RECIST 1.1. PFS1 is defined as the time from randomization to disease progression and will be primarily used for the formal hypothesis test.;Timepoint(s) of evaluation of this end point: PFS1 is defined as the time from randomization to disease progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression-free survival after initiation of second-line therapy (PFS2) - Overall survival after initiation of second-line therapy (OS) - Objective response rate (ORR) - best overall response during second linetreatment - Subgroup analysis: Objective response rate (best overall response) after randomization - Duration of response (DoR) - TFST (Time to first subsequent treatment): Time from initiation of second line treatment to initiation of third line treatment. - Tolerability and adverse events - Quality of life - Biomarkers;Timepoint(s) of evaluation of this end point: The nomenclature of the efficacy endpoint is defined in a way that the suffix “1” indicates the time from randomization, whereas the suffix “2” indicates the time from initiation of second line treatment. Both timepoints have been chosen in order to i) guarantee comparability with published data and ii) to address the question to which extent patients benefit from the experimental treatment. | — |
Countries
Germany
Contacts
Public ContactAIO-Studien-gGmbH
AIO-Studien-gGmbH
Outcome results
None listed