SHS_492323 WESH CGEN 15212

A Phase III, Open-label, Randomized Study to Investigate the Efficacy and Safety of MPDL3280A (Anti-PD-L1 Antibody) Compared With Best Supportive Care Following Adjuvant Cisplatin-based Chemotherapy in PD-L1-Selected Patients With Completely Resected Stage IB-IIIA Non-small Cell Lung Cancer

The primary efficacy objective of the study is to evaluate the efficacy of 16 cycles of Atezolizumab (MPDL3280A) treatment compared with best supportive care as measured by disease-free survival (DFS) as assessed by the investigator.

Inclusion Criteria for Enrollment Phase

•ECOG performance status of 0 or 1
•Histological or cytological diagnosis of Stage IB (tumors >/= 4 cm) -IIIA (T2-3 N0, T1-3 N1, T1-3 N2) NSCLC
•Patients must have had complete resection of NSCLC 6-12 weeks (>/= 42 days and •Complete mediastinal lymph node dissection (MLND) is required
•Eligible to receive a cisplatin-based chemotherapy regimen
•Adequate hematologic and end-organ function as defined by lab values listed in the protocol

Select Inclusion Criteria for Randomized Phase

•Women who are not postmenopausal (>/= 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug or BSC

Select Exclusion Criteria for Enrollment Phase

•Treatment with prior systemic chemotherapy at any time
•Hormonal cancer therapy or radiation therapy as prior cancer treatment within 5 years before enrollment
•Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrollment
•Patients with hearing impairment
•Known sensitivity to any component of the chemotherapy regimen the patient will be assigned to or to mannitol
•Prior treatment with an anti-PD-1, anti-PD-L1, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
•Interstitial lung disease or history of pneumonitis
•Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death
•History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
•Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation
•History of autoimmune disease
•Positive test for HIV
•Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
•Active tuberculosis
•Significant cardiovascular disease
•Prior allogeneic bone marrow transplantation or solid organ transplant

Specific Exclusions for Pemetrexed Treatment

•Patients with squamous cell histology
•Patients who are receiving concurrent nonsteroidal anti-inflammatory agents (NSAIDs) and are unable to discontinue treatment

Select Exclusion Criteria for Randomized Phase

•Signs or symptoms of infection within 14 days prior to randomization
•Received therapeutic oral or IV antibiotics within 14 days prior to randomization
•Major surgical procedure within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
•Administration of a live, attenuated vaccine within 28 days prior to randomization or anticipation that such a live attenuated vaccine will be required during the study
•Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to randomization
•Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium >ULN)
•For patients who are receiving denosumab prior to randomization, unwillingness or ineligibility to receive a bisphosphonate instead while in the study
Phase III
NCT02486718
Cancer
Lung
Howard (Jack) West, M.D.
Genentech
Andrew Smith
  • Swedish Medical Center