A Phase 1b/2 Study of Safety and Efficacy of Rociletinib in Combination With MPDL3280A in Patients With Advanced or Metastatic EGFR-mutant NSCLC

Inclusion Criteria:

ECOG performance status of 0 or 1
Adequate hematological and biological function, confirmed by defined laboratory values
Histologically or cytologically documented metastatic or unresectable, locally advanced or metastatic NSCLC, with one or more activating EGFR mutation (eg, G719X, exon 19 deletion, L858R, L861Q) and absence of exon 20 insertion
Measurable disease as defined by RECIST v1.1
Biopsy of tumor tissue for central evaluation, within 60 days prior to the first day of study treatment
For Phase 1 and Phase 2 Group B, progression after prior 1st or 2nd generation EGFR TKI (eg, erlotinib, gefitinib, afatinib). Previous chemotherapy for NSCLC is allowed.
For Phase 2 Group A, EGFR TKI treatment-naïve and chemotherapy-naïve

Exclusion Criteria:

Unresolved toxicities from prior therapy
Symptomatic, untreated or unstable central nervous system or leptomeningeal metastases
Previous treatment with rociletinib or MPDL3280A, or other 3rd generation EGFR TKI (eg, AZD-9291, HM61713), or PD 1 axis targeted therapy (eg, anti PD 1 or anti-PD L1)
Prior treatment with CD137 agonists or other immune checkpoint blockade therapies, including anti-CTLA-4 therapeutic antibodies
Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures
Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab (bisphosphonate use for prevention of skeletal events allowed)
Known hypersensitivity to any component of the MPDL3280A or rociletinib formulations or history or hypersensitivity to chimeric humanized antibodies or fusion proteins
History of autoimmune disease
History of prior allogeneic hematopoietic stem cell transplantation or prior solid organ transplantation
Treatment with systemic immunosuppressive medications within 2 weeks prior to first day of study treatment (inhaled corticosteroids and mineralocorticoids allowed)
Live attenuated vaccine within 4 weeks prior to first day of study treatment
Active tuberculosis, active hepatitis, or positive HIV status
Class II to IV heart failure as defined by the New York Heart Association functional classification system
Untreated or uncontrolled cardiovascular disease or other symptomatic cardiac dysfunction
QTCF > 450 ms, inability to measure QT interval on ECG, personal or family history of long QT syndrome, requirement for medications that have the potential to prolong the QT interval
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan (history of radiation pneumonitis in radiation field may be allowed)
Other malignancies within 5 years prior to enrollment, with the exception of carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ