Early Stage Resectable Non-small cell lung cancer (NSCLC) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age >= 18 years • Ability to comply with the study protocol, in the investigator's judgment • Pathologically documented Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology Staging should be based on the 8th edition of the American Joint Committee on Cancer / Union Internationale Contre le Cancer NSCLC staging system - T4 primary NSCLC will be allowed only on the basis of size (tumors > 7 cm). Invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodules in a different ipsilateral lobe is not permitted - Patients with mixed NSCLC histology or NSCLC not otherwise specified are eligible - Patients may be screened based on clinical stage, but mandatory preoperative documentation of N2 nodal involvement by invasive mediastinal staging is required for N2 PET positive nodes. Pre-operative staging of levels 5/6 nodes is optional. • Solid or subsolid appearance of NSCLC on CT scan with no appearance of purely ground-glass opacity (GGO) For subsolid lesions, the tumor size should be measured based on solid component only, exclusive of the GGO component. • Evaluation by the operating attending surgeon and involved medical oncologist prior to study enrollment to verify study eligibility for R0 resection with curative intent • Adequate pulmonary function to be eligible for surgical resection with curative intent, as assessed by Pulmonary function tests (PFTs) performed within 6 months of planned resection and repeated at screening, if clinically indicated, including lung volumes, spirometry, and a diffusion capacity and meeting at least one of the following criteria: - Predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) and ppo diffusion capacity (DLCO).>=40% - Maximal oxygen consumption (VO2max) >=15 mL/kg/min • If either ppo FEV1 or ppo DLCO is = 15 mL/kg/min If PFTs were performed before 6 months of planned resection or have never been performed, they must be performed during the screening period • Adequate cardiac function to be eligible for surgical resection with curative intent • Measurable disease as assessed by the investigator per RECIST v1.1 • Eligibility to receive a platinum-based chemotherapy regimen • Availability of a representative tumor specimen suitable for determination of PD-L1 status via central testing • Eastern Cooperative Oncology Group Performance Status of 0 or 1 • Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: - Absolute neutrophil count >= 1.5 × 109/L (1500/µL) without granulocyte colony-stimulating factor support - Lymphocyte count >= 0.5 × 109/L (500/µL) - Platelet count >= 100 × 109/L (100,000/µL) without transfusion - Hemoglobin >= 90 g/L (9.0 g/dL) Patients may be transfused to meet this criterion. - Aspartate transaminase Test, Alanine aminotransferase Test, and Alkaline phosphatase level = 45 mL/min - For patients intended to receive cisplatin: creatinine clearance >= 60 mL/min - Serum albumin >= 25 g/L (2.5 g/dL) - For patients not
Exclusion criteria
Exclusion criteria: • Illness or condition that may interfere with a patient’s capacity to understand, follow, and/or comply with study procedures • Any prior therapy for lung cancer, including chemotherapy, or radiotherapy • Major surgical procedure, other than for diagnosis, within 28 days prior to initiation of study treatment, or anticipation of need for non-protocol-mandated major surgical procedure during the study • Activating mutation in the epidermal growth factor receptor or with an anaplastic lymphoma kinase (ALK) fusion oncogene • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis • History of idiopathic pulmonary fibrosis, organizing pneumonia drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan • Active tuberculosis • Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina • History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment • Prior allogeneic stem cell or solid organ transplantation • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab • Current treatment with anti-viral therapy for HBV • Treatment with investigational therapy within 42 days prior to initiation of study treatment • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug prior to initiation of study treatment • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation • Known allergy or hypersensitivity to any component of the chemotherapy regimen the patient will be assigned to • For patients intended to receive cisplatin, any hearing impairment • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after last dose of atezolizumab, 30 days after the last dose of nab-paclitaxel, or 6 months after last dose of pemetrexed, gem
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy based on central pathology-assessed major pathological response (MPR) • To evaluate the efficacy of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy followed by adjuvant atezolizumab based independent review facility -assessed event-free survival (EFS);Secondary Objective: To evaluate: • The efficacy of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy followed by adjuvant atezolizumab based on, overall survival (OS), investigator-assessed EFS, IRF-assessed EFS by PD-L1 expression, 2 and 3-year OS and investigator-assessed EFS, disease-free survival (DFS) • The efficacy of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy based on objective response rate, centrally-assessed pathological complete response (pCR), investigator-assessed MPR and pCR • Patient reported outcome of GHS/HRQoL associated with atezolizumab in combination with platinum-based chemotherapy • The safety of neoadjuvant treatment with atezolizumab in combination with platinum-based chemotherapy followed by adjuvant atezolizumab • The immune response to atezo • The pharmacokinetic (PK) profile of atezolizumab when given in combination with platinum-based chemotherapy and PK profile of atezolizumab alone;Primary end point(s): 1. MPR, as assessed by central pathology laboratory 2. EFS, as assessed by the IRF;Timepoint(s) of evaluation of this end point: 1. Up to 26 months 2. Up to 82 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. OS 2. Investigator-assessed EFS 3. IRF-assessed EFS by PD-L1 expression 4. Objective response by the investigator according to RECIST v1.1 5. pCR, as assessed by central pathology laboratory 6. MPR and pCR, as assessed by the investigator site pathology laboratory 7. 2-year and 3-year OS and investigator-assessed EFS 8. DFS as determined by the investigator 9. Change from baseline in health-related quality of life (HRQoL) scores as assessed through use of the two-item global health status (GHS)/HRQoL subscale (Questions 29 and 30) of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 at each assessment timepoint during the study through the completion of adjuvant treatment and observation follow up assessments 10. Occurrence and severity of adverse events, including serious adverse events and immune-related adverse events, with severity determined according to NCI CTCAE v5.0 11. Pharmacokinetics and pharmacodynamics of atezolizmab 12. Incidence of anti-drug antibodies (ADAs) against atezolizumab during the study;Timepoint(s) of evaluation of this end point: 1-3. Up to 82 months 4. Up to 4 months 5-6. Up to 26 months 7. At 2 and 3 year 8-11. Up to 82 months 12-13. Day 1 of Cycles 1 and 3; Day 1 of Cycles5, 7, 11, and 19; at disease progression/recurrence or treatment/observation follow-up discontinuation visit (<=30 days after last dose) | — |
Countries
Australia, Austria, Brazil, China, Costa Rica, France, Germany, Guatemala, Hungary, Israel, Italy, Korea, Republic of, Mexico, Panama, Peru, Poland, Slovenia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed