Patients with stage IIIB/IV non-squamous non-small cell lung cancer with EGFR mutations, ALK rearrangement or ROS1 fusion progressing after targeted therapies MedDRA version: 21.1 Level: PT Classification code 10029515 Term: Non-small cell lung cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Centre François Baclesse
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patient older than 18 years and no more than 75 year-old • Subject affiliated to an appropriate social security system • Signed informed consent before any trial related activities and according to local guidelines • ECOG performance status of 0 or 1 • Histologically or cytologically confirmed, stage IIIB/IV non-squamous NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 7th edition) • Patient with a sensitizing mutation in the EGFR gene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more EGFR TKIs, such as erlotinib, gefitinib, osimertinib or another EGFR TKI appropriate for the treatment of EGFR-mutant NSCLC • Patient with an ALK fusion oncogene (confirmed in local laboratory) must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e., crizotinib, alectinib, ceritinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene • Patient with a ROS1 fusion oncogene (confirmed in local laboratory) must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ROS inhibitors (i.e., crizotinib,) appropriate for the treatment of NSCLC in patients having an ROS1 fusion oncogene • No prior chemotherapy treatment for Stage IV non-squamous NSCLC except if less than 3 cycles, with treatment free-interval of at least 1 year from inclusion since last chemotherapy • Patient who has received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from inclusion since the last chemotherapy, radiotherapy, or chemoradiotherapy • Patient with an history of treated asymptomatic CNS metastases is eligible •Measurable disease, as defined by RECIST v1.1 •Adequate hematologic and end-organ function •Adequate method of contraception during the treatment period and at least 5 months after the last dose of atezolizumab or 6 months after the last dose of chemotherapy 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 149 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 149
Exclusion criteria
Exclusion criteria: • Active or untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments • Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for = 2 weeks prior to inclusion • Leptomeningeal disease • Uncontrolled tumour-related pain • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently); Patients with indwelling catheters (e.g., PleurX®) are allowed. • Uncontrolled or symptomatic hypercalcemia (>1.5 mmol/L ionized calcium or calcium >12 mg/dL or corrected serum calcium > ULN) • Patients who are receiving denosumab prior to inclusion must be willing and eligible to discontinue its use and replace it with a bisphosphonate instead. • Malignancies other than NSCLC within 5 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent) • Women and men under efficient contraception during treatment and at least 6 months after the end of all the treatments; • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjo¨gren’s syndrome, Guillain-Barre´ syndrome, multiple sclerosis, vasculitis, or glomerulonephritis • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan; History of radiation pneumonitis in the radiation field (fibrosis) is permitted. • Positive test for HIV. All patients will be tested for HIV prior to inclusion into the study; patients who test positive for HIV will be excluded from the study. • Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible only if they are negative for HBV DNA. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA. • Active tuberculosis • Severe infections within 4 weeks prior to inclusion, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia • Received therapeutic oral or IV antibiotics within 2 weeks prior to inclusion; Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chroni
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of the combination of Platinum (carboplatin or cisplatin), Pemetrexed, Atezolizumab ? Bevacizumab if eligible, in stage IIIB/IV non-squamous non-small cell lung cancer patients with progression-enhancing mutations following targeted therapies. Efficacy will be defined as the objective response rate (ORR) after 4 cycles of treatment. Two distinct cohorts will be considered as follows since they will allow bringing separate information ;Secondary Objective: To assess in each cohort • The progression-free survival (PFS) • The duration of response (DOR) • The time to deterioration (TTD) • The change from baseline in patient-reported lung cancer symptoms (chest pain, dyspnoea, and cough) scores • The ORR according to immune RECIST (iRECIST) criteria • The overall survival (OS) • The OS rate at 1 and 2 years • The tolerance profile of the combination in the induction phase and the maintenance phase of treatment Creation of a biological collection for ancillary analysis (To look at the correlation between PD-L1 expression levels, Tumor Mutation Burden (TMB) expression and antitumor activity). ;Primary end point(s): Objective response rate (ORR), defined as the proportion of patients who achieved an objective response after 4 cycles of induction (or before progression). Objective response will be considered in case of radiologically confirmed complete (CR) or partial response (PR) according to RECIST v1.1 criteria (Response Evaluation Criteria in Solid Tumors version 1.1) assessed by masked, independent central review ;Timepoint(s) of evaluation of this end point: Progression of disease | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression-free survival, defined as the time relapsed between inclusion and disease progression (according to RECIST v1.1 criteria as assessed by the investigator) or death from any cause, whichever occurs first • Duration of response assessed in patients who had an objective response as determined by the investigator using RECIST v1.1 and defined as the time interval from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented, whichever occurs first • Time to deterioration in lung-related symptoms, defined as the time from inclusion to the time the patient’s score on the EORTC QLQ C30 or QLQ-LC13 shows a =10-point increase above baseline in each of the following EORTC-transformed scores for cough, dyspnea (single item), dyspnea (multi-item subscale) and chest pain. • Objective response rate according to immune (i)RECIST criteria defined similarly as ORR, with the exception that immune RECIST criteria 2017 are used instead of RECIST v 1.1 • Overall survival, defined as the time between the date of inclusion and death from any cause • Toxicities occurring during either the induction or maintenance treatment in terms of kind, grade, time of onset, reversibility, according to NCI-CTCAE v5.0 criteria ;Timepoint(s) of evaluation of this end point: - survival rate (overall and progression-free) - treatment tolerance assessed throughout the study - quality of life at inclusion, every 2 cycles, end of treatment then every 3 cycles | — |
Countries
France
Contacts
Public ContactOlivier BYLICKI
HIA PERCY
Outcome results
None listed