Advanced (stage IIIB/IIIC/IV) NSCLC patients eligible for treatment with a PD-1 or PD-L1 antagonist according to the European Marketing Authorisation in a first line or a second line
Conditions
Interventions
Trade Name: Tecentriq
Product Name: Atezolizumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44
Concentration unit: mg/ml milligram(s)/millilitre
C
Sponsors
UNICANCER
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient must have signed a written informed consent form prior to any study specific procedures 2. Histologically or cytologically confirmed advanced (stage IIIBI/IIIC//IV), squamous or non-squamous NSCLC 3. Availability of tumoral PD-L1 status if pembrolizumab used (for the other drugs if possible tumoral PD-L1 status or tumor sample to assess it) 4. First-line treatment and non-squamous histology: documentation of targetable tumor mutations, activating EGFR mutations and ALK gene rearrangements 5. First-line treatment only: NSCLC patients eligible for treatment with pembrolizumab according to the European Marketing Authorisation as a first line: a. no EGFR or ALK positive tumour mutations. b. Tumoral expression of PD-L1 = 50% 6. Second (third)-line treatment: NSCLC patients eligible for treatment with a PD-1 or PD-L1 antagonist according to the European Marketing Authorisation as a second line: a. Previous treatment with chemotherapy and/or targeted treatment b. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving nivolumab, pembrolizumab or atezolizumab; PD-L1 >1% for patients receiving pembrolizumab; any tumoral PD-L1 status for those receiving nivolumab or atezolizumab 7. Second line treatment : non-radically treatable stage IIIB/C or IV disease that has progressed on or after platinum-based chemotherapy and/or targeted therapy (targeting ALK translocation or EGFR mutation 8. Patient =18 and =80 years of age. 9. ECOG performance status 0 – 1 10. Life expectancy >3 months 11. Measurable lesion as assessed by RECIST version 1.1. 12. Metastases eligible for 3 dimensional conventional radiotherapy (3D-CRT) or stereotactic ablative radiotherapy (SABR) in terms of dose constraints at organ at risk (according to QUANTEC review) 13. Patients must have adequate organ function defined by the following laboratory results obtained within 14 days prior to the first study treatment: a. absolute neutrophil count of =1 500 /mm3, b. platelets = 100 000/mm3, c. haemoglobin >9 g/dL (transfusions allowed), d. creatinine clearance >30 mL/min e. bilirubin =1.5 X ULN (unless Gilbert where 3 X ULN is permitted) f. serum ALT and AST =2.5 X ULN (unless documented liver metastasis where =5 X ULN is permitted) g. ALP =2.5 X ULN (unless documented bone or liver metastasis where =5X ULN is permitted). h. INR , PT, PTT =1.5 X ULN (unless the subject is receiving anticoagulant therapy) 14. Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 6 months after completing treatment/therapy 15. Patients affiliated to the social security system 16. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, and examinations including follow-up. 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 267 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 243
Exclusion criteria
Exclusion criteria: 1. Prior therapy with T-cell costimulation or checkpoint-targeted agents 2. Clinical need of radiotherapy (e.g.: whole brain irradiation, painful metastasis, bleeding, compressive metastases) 3. Leptomeningeal carcinomatosis, or metastases with indistinct borders making targeting not feasible 4. Patient with evidence of active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patient with brain metastasis can be included if asymptomatic and not requiring steroids 5. Metastases located within 3 cm of the previously irradiated structures (EQD2doses): a. Spinal cord previously irradiated to >40 Gy; b. Brachial plexus previously irradiated to >50 Gy; c. Small intestine, large intestine, or stomach previously irradiated to >45 Gy; d. Brainstem previously irradiated to >50 Gy; e. Lung previously irradiated with prior V20Gy >30% 6. Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, psoriasis 7. Symptomatic interstitial lung disease 8. Systemic immunosuppression or systemic immunosuppressive medicinal products within 2 weeks prior to study entry. 9. Concomitant treatment with steroids (equivalent dose of prednisone >10 mg/kg) treatment: otherwise it has to be stopped 7 days before inclusion. 10. Prior invasive malignancy within the past 2 years (except non-melanomatous skin cancer non-invasive carcinoma in-situ of the breast, oral cavity, bladder or cervix) 11. Known Acquired Immune Deficiency Syndrome (AIDS) or severe uncontrolled co-morbidity 12. Active hepatitis B or C 13. Patient who was administered a live, attenuated vaccine within 28 days prior to enrolment 14. Patient with any other disease or illness which requires hospitalisation or is incompatible with the study treatment are not eligible. Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study 15. Patient who have taken any investigational medicinal product or have used an investigational device within 30 days of inclusion 16. Pregnant or breast feeding woman 17. Person deprived of their liberty or under protective custody or guardianship
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare Overall Survival (OS) rate between anti-PD-(L)1 versus anti-PD-(L)1 + radiotherapy with report of 1 year and 2 years rates;Secondary Objective: To compare between the two arms: -Cause of death -Toxicities according to CTCA version 5 -Progression Free Survival (PFS) with report of 1 and 2 year rates -Cancer Specific Survival (CSS) with report of 1 and 2 year rates -In irradiated patients: local and distant control with report of 6 months and 1-year rates in irradiated and non-irradiated sites, respectively. -Quality of life according to QLQ-C30;Primary end point(s): The primary endpoint of this trial is overall survival (OS) defined as the time from randomization to the date of documented death from any cause or last follow-up. OS rate will be reported at 1 and 2 years. ;Timepoint(s) of evaluation of this end point: Overall Survival rate will be reported at 1 and 2 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Acute/ late toxicity will be assessed according to the flowchart and graded by CTCAE v5 (toxic death and serious adverse events) Tumour response is defined as the percentage of patients with a complete response (CR) or partial response (PR), according to RECIST 1.1 and iRECIST (centralized response evaluation). Progression-free survival (PFS) is defined as the time from randomization until documented disease progression (PD) according to RECIST 1.1 and iRECIST (centralized response evaluation for both arms), or death, whichever occurs first. PFS rate will be reported at 1 & 2 years Cancer specific survival (CSS) is defined as the time from randomization to documented death from cancer from the treatment. CSS rate will be reported at 1 & 2 years. Local and distant controls in irradiated patients are defined as the time from randomization to the first documented local event or distant event. Control rates will be reported at 6 months and 1 years Quality of life will be assessed using self-administered questionnaires (EORTC QLQ-C30) according to the flowchart. ;Timepoint(s) of evaluation of this end point: The percentage of patients with a complete response (CR) or partial response (PR). Progression Free Survival rate will be reported at 1 & 2 years. Cancer Specific Survival rate will be reported at 1 & 2 years. Control rates will be reported at 6 months and 1 years | — |
Countries
France
Contacts
Public ContactProject Manager, Naima BONNET
UNICANCER
Outcome results
None listed