A multicentre phase II, open-label, non-randomized study evaluating Platinum-Pemetrexed-Atezolizumab (? Bevacizumab) for patients with stage IIIB/IV non-squamous non-small cell lung cancer with EGFR mutations, ALK rearrangement or ROS1 fusion progressing after Targeted therapies

Phase 1

Active, not recruiting

• Conditions: 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: 21.1Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000727-41-FR
• Lead Sponsor: Centre François Baclesse

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-07-29
• Last Update Posted: 3 November 2021

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 149

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

• 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified