Atezolizumab and Tiragolumab in Patients With NSCLC or Advanced Solid Tumors Having Had Prior Treatment With a PD-1 Inhibitor

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 - 2
• Adequate hematologic function defined as:
• Absolute neutrophil count (ANC) ≥1500/μL with one exception: Patients with benign ethnic neutropenia (BEN): ANC >1300/ μL
• Lymphocyte count ≥0.5 × 109/L (500/µL)
• Hemoglobin (Hgb) ≥9 g/dL (patients may be transfused to meet this criterion)
• Platelets ≥100, 000/µL (without transfusion, within 7 days of enrollment)
• Adequate liver function defined as:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN)
• Total bilirubin ≤1.5 x ULN (patients with known Gilbert syndrome: serum bilirubin level ≤ 3 x ULN)
• Adequate renal function defined as serum creatinine ≤1.5 mg/dL (133 μmol/L) or calculated creatinine clearance ≥30 mL/min as calculated by the Cockcroft Gault formula
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤1.5 × ULN. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of /=1%

Crossover from Arm A to Arm B

• Last dose of atezolizumab is >/=21 days

Inclusion Arm B - Advanced solid tumors 19. Patients with advanced RCC progressing on anti-PD-1 therapy, Advanced TNBC progressing on anti-PD-1 therapy, and patients with NSCLC progressing on check-point inhibitors plus chemotherapy in the first-line setting. MSI-high solid tumors as defined by local testing for MSI/MMR will also be included.

• Evidence of disease progression after receiving clinical benefit, defined as having at least one scan demonstrating at least SD, during most recent PD-1 inhibitor treatment.

Exclusion Criteria

• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• History of any Grade 3 or 4 toxicities to a prior CPI treatment
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulations
• Most recent immunotherapy ≤21 days and ≥ Grade 2 immunotherapy-related side effects, with the exception of alopecia.
• Use of systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) ≤28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drugs.
• Treatment with chemotherapy in the first line setting.7. Treatment with investigational therapy within 28 days prior to initiation of study treatment.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF- agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study, with the following exceptions:
• Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
• Patients who received mineralocorticoids (e.g., fludrocortisone), inhaled corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the course of the study or within 5 months after the last dose of atezolizumab or tiragolumab 10. Uncontrolled tumor-related pain 11. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment.
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary