Non-squamous non-small cell lung cancer MedDRA version: 19.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Product Name: Atezolizumab
Product Code: Ro 554-1267/F03-01
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Atezolizumab
Current Sponsor code: RO5541267
Other descriptive name: MPDL328
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female, 18 years of age or older - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Histologically or cytologically confirmed, Stage IV non-squamous NSCLC - No prior treatment for Stage IV non-squamous NSCLC - Patients who have 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 randomization since the last dose of chemotherapy and/or radiotherapy. - Measurable disease, as defined by RECIST v1.1 - Adequate hematologic and end organ function - For enrollment into the China extension phase, residence in the People’s Republic of China - For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 194
Exclusion criteria
Exclusion criteria: Cancer-Specific Exclusions - Patients with a sensitizing mutation in the EGFR gene or an ALK fusion oncogene - Active or untreated CNS metastases as determined by computed tomography (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 randomization - Leptomeningeal disease - Uncontrolled tumor-related pain - Uncontrolled or symptomatic hypercalcemia (> 1.5 millimole/Liter ionized calcium or calcium > 12 milligram/deciliter or corrected serum calcium > upper limit of normal) - Malignancies other than NSCLC within 5 years prior to randomization - Known tumor PD-L1 expression status from other clinical studies General Medical Exclusions: - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - History of certain autoimmune disease - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis - Severe infections within 4 weeks prior to randomization - Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina Exclusion Criteria Related to Medications and Chemotherapy: - Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, 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 randomization - Treatment with systemic immunosuppressive medications Exclusion Criteria Related to Chemotherapy: - History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds - Patients with hearing impairment (cisplatin) - Grade >= 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 criteria (cisplatin) - Creatinine clearance (CRCL) =< 60 milliliter (mL)/minute (min) for cisplatin or < 45 mL/min for carboplatin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of atezolizumab (atezo) as measured by investigator-assessed progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in atezolizumab + carboplatin + pemetrexed versus carboplatin + pemetrexed •To evaluate the efficacy of atezo as measured by overall survival (OS);Secondary Objective: To evaluate o Efficacy of atezo as measured by Independent Review Facility-assessed PFS using RECIST v1.1 o Efficacy of atezo as measured by investigator-assessed objective response rate, duration of response, time to response, time in response according to RECIST v1.1 o OS rate at 1 and 2 years o Safety and tolerability of atezo when given in combination with carboplatin or cisplatin + pemetrexed or as maintenance therapy with pemetrexed alone o Incidence and titers of anti-therapeutic antibody against atezo and to explore the potential relationship of the immunogenicity response with pharmacokinetics (PK), safety, and efficacy o Impact of atezo as measured by time to deterioration (TTD) in patient-reported lung cancer symptoms To characterize o PK of atezo when given with carboplatin or cisplatin + pemetrexed or pemetrexed alone o PK of carboplatin and cisplatin when given with atezo and Pemetrexed o PK of pemetrexed when given with atezo + carboplatin or cisplatin ;Primary end point(s): 1. Progression free survival as assessed by the investigator 2. Overall Survival ;Timepoint(s) of evaluation of this end point: 1 and 2: Up to 45 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS as assessed by IRF Objective Response 2. Duration of Response 3. Time to Response 4. Time in Response 5. Overall Survival rate at years 1 and 2 6. Time to deterioration in patient-reported lung cancer symptoms using each of the EORTC QLQ-C30 and the supplemental lung cancer module EORTC QLQ-LC13 7. Time to deterioration in patient-reported lung cancer symptoms (cough, dyspnea, or chest pain, whichever occurs first) with use of the SILC scale symptom score 8. Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.0 9. Maximum observed serum atezo concentration after infusion (Arm A) 10. Minimum observed serum atezo concentration prior to infusion (Arm A) 11. Plasma concentrations for carboplatin or cisplatin (Arm A) 12. Plasma concentrations for pemetrexed (Arm A) ;Timepoint(s) of evaluation of this end point: 1-4. Up to 45 months 5. At 1 and 2 years 6-8. Up to 45 months 9-10. C1D1, C2D1, C3D1, C4D1, C8D1, C16D1, after C16 every eighth cycle D1, at treatment discontinuation, 120 (+/-30) days after last dose of atezolizumab 11-12. C1D1, C3D1 | — |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Chile, Croatia, France, Hong Kong, Hungary, Israel, Italy, Latvia, Lithuania, Malaysia, Netherlands, Peru, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed