None listed
Conditions
Interventions
Dosage, Administration and compliance: Study treatment will be assigned by the IxRS. Splitting into 2 phases, Induction phase and maintenance phase.
The induction phase of the study will consist o
Arm A:
MPDL3280A 1200 mg intravenous (IV) infusion Over 60 (± 15) min for the first infusion
30 (± 10) min for subsequent infusions if it was tolerated in the first infusion of the cycle 1 + carboplatin administered to get an area under the curve (AUC) objective initial of 6mg/ml/min IV
30 min + Paclitaxel 200mg/m2 (15mg /kg) IV infusion over 180 minutes D1
▪
Arm B:
MPDL3280A 1200 mg intravenous (IV) infusion Over 60 (± 15) min for the first infusion
30 (± 10) min for subsequent infusions if it was tolerated in the first infusion of the cycle 1 + carboplatino administered to get an area under the curve (AUC) objective initial of 6mg/ml/min IV
30 min + Nab Paclitaxel 100mg/m2 IV infusion Over 30 minutes D1, D8, D15
▪
Arm C:
Carboplatin administered to get an area under the curve (AUC) objective initial of 6mg/ml/min IV Over approximately 15 - 30
Following the induction phase, patients randomized to MPDL328
Sponsors
F. HOFFMANN-LA ROCHE LTD.,
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: ▪ Signed Informed Consent Form ▪ Male or female, 18 years of age or older ▪ ECOG performance status of 0 or 1 (see Appendix 10) ▪ Histologically or cytologically confirmed, Stage IV squamous NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 7th edition; Detterbeck et al. 2009; see Appendix 3). ▪ No prior treatment for Stage IV squamous NSCLC: Patients with a sensitizing mutation in the EGFR gene must have experienced disease progression (during or after treatment) or intolerance to treatment with erlotinib, gefitinib, or another EGFR tyrosine kinase inhibitor (TKI) appropriate for the treatment of EGFR-mutant NSCLC. Patients with an ALK fusion oncogene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e. crizotinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene. ▪ Patients who have received prior neo-adjuvant, adjuvant chemotherapy, 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 chemotherapy or completion of chemoradiotherapy. ▪ Patients with a history of treated asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: □ Measurable disease outside CNS, Only supratentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord) No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed, No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization, No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. □ Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to enrollment, if all other criteria are met. ▪ Known PD-L1 tumor status as determined by an IHC assay performed by a central laboratory on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening. □ A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or a minimum of 15 unstained, freshly cut, serial sections from an FFPE tumor specimen is required for participation in this study. This specimen must be accompanied by the associated pathology report. Fine-needle aspiration, brushing, cell pellet specimens (e.g., from pleural effusion, and lavage samples) are not acceptable. □ Tumor tissue from bone metastases is not acceptable. For core needle biopsy specimens, at least three cores, preferably embedded in a single paraffin block, should be submitted for evaluation. □ If fewer than 15 slides are available at baseline (but no fewer than 10), the patient may still be eligible, upon discussion with the Medical Monitor. ▪ Measurable disease, as defined by RECIST v1.1 Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site
Exclusion criteria
Exclusion criteria: Cancer-Specific Exclusions ▪ Active or untreated CNS metastases as determined by CT or 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 □ Patients requiring pain medication must be on a stable regimen at study entry. □ Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. □ Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy if appropriate prior to randomization. ▪ 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 Ca  12 mg/dL or corrected serum calcium  ULN) □ Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study. ▪ Malignancies other than NSCLC within 5 years prior to randomization, 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) ▪ Known tumor PD-L1 expression status from other clinical trials (e.g., patients whose PD-L1 expression status was determined during screening for entry into a trial with anti-programmed death-1 [PD-1] or anti-PD-L1 antibodies but were not eligible are excluded) General Medical Exclusions ▪ Women who are pregnant, lactating or intending to become pregnant during the study ▪ 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 cell products or any component of the MPDL3280A 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, Sjögren’s syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis □ Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. □ Patients with controlled type I diabetes mellitus on a stable dose of insu
Countries
Argentina, Australia, Austria, Belgium, Canada, France, Israel, Japan, Latvia, Lithuania, Portugal, Russian Federation, Singapore, Spain, Switzerland, Taiwan, Ukraine, United States
Contacts
Public ContactAndres Bayona
PPD Peru S.A.C.
Outcome results
None listed