Atezolizumab with and without Tiragolumab with Chemotherapy in Treating Patients with Esophageal or Gastroesophageal Cancer

Inclusion Criteria

• Signed informed consent form
• Age >= 18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol, in the investigator’s judgment
• Histologically or cytologically confirmed esophageal or gastroesophageal type I or II adenocarcinoma
• No prior therapy including chemotherapy or radiation therapy
• Patients with T1N1, and T2-3 with any N will be eligible
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1500/uL) without granulocyte colony-stimulating factor support (obtained within 14 days prior to initiation of study treatment)
• Lymphocyte count >= 0.5 x 10^9/L (500/uL) (obtained within 14 days prior to initiation of study treatment)
• Platelet count >= 100 x 10^9/L (100,000/uL) without transfusion (obtained within 14 days prior to initiation of study treatment)
• Hemoglobin >= 90 g/L (9 g/dL); patients may be transfused to meet this criterion (obtained within 14 days prior to initiation of study treatment)
• Aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN) (obtained within 14 days prior to initiation of study treatment)
• Alanine aminotransferase (ALT) =< 2.5 x ULN (obtained within 14 days prior to initiation of study treatment)
• Alkaline phosphatase (ALP) =< 2.5 x ULN (obtained within 14 days prior to initiation of study treatment)
• Serum bilirubin =< 1.5 x ULN with the following exception: * Patients with known Gilbert disease: serum bilirubin level =< 3 x ULN (obtained within 14 days prior to initiation of study treatment)
• Serum creatinine =< 1.5 x ULN [or] creatinine clearance >= 70 mL/min (calculated using the Cockcroft-Gault formula) (obtained within 14 days prior to initiation of study treatment)
• Serum albumin >= 25 g/L (2.5 g/dL) (obtained within 14 days prior to initiation of study treatment)
• For patients not receiving therapeutic anticoagulation: international normalized ratio (INR) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN (obtained within 14 days prior to initiation of study treatment)
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Medically fit for surgery based on surgeon’s assessment.
• No supraclavicular, or para-aortic nodal enlargement unless biopsy negative
• Male or female but both sexes must practice adequate contraception while on therapy
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 14 days prior to the start of study drug. Women must not be breastfeeding * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: ** With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for for 90 days after the final dose of tiragolumab, 6 months after the final dose of oxaliplatin and 5-FU to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
• Availability of a representative tumor specimen that is suitable for PDL-1 testing at MD Anderson (MDA). * A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study enrollment. If < 10 slides are available, the patient may still be eligible for the study, after principal investigator approval has been obtained. For Cohort 1: If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening.

Exclusion Criteria

• Patients with T1aN0, T4b, or M1 cancer will be excluded
• Squamous cell carcinoma histology
• Invasion into nearby organs (T4b) with or increased risk for fistula
• Significant comorbid conditions (defined as uncontrolled diabetes, active angina or heart failure, uncontrolled hypertension [>160 mmHg systolic or >=100 mmHg diastolic], ) or increased risk of prolonged QTc (QTc > 500 ms), active psychiatric condition that prevents consistent participation and compliance)
• More than grade 1 neuropathy
• Unable to comprehend the requirements of the study or comply with it
• Active bleeding from primary tumor requiring radiation therapy
• History of leptomeningeal disease
• Uncontrolled tumor-related pain * Patients requiring pain medication must be on a stable regimen at study entry. * Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy 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 that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) *Patients with indwelling catheters (e.g., PleurX [registered trademark]) are allowed.
• Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN)
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren’s syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions: Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study. Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: * Rash must cover < 10% of body surface area * Disease is well controlled at baseline and requires only low-potency topical corticosteroids * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Positive human immunodeficiency virus (HIV) test at screening
• Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening
• Patients with a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening, are eligible for the study
• Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test
• Active tuberculosis
• Significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
• History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS of > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety.
• 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 disease exacerbation) are eligible for the study
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Prior allogeneic stem cell or solid organ transplantation
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment, within 90 days after the final dose of tiragolumab, or within 5 months after the final dose of atezolizumab
• Positive Epstein-Barr virus (EBV) viral capsid antigen immunoglobulin M (IgM) test at screening *An EBV PCR test should be performed as clinically indicated to screen for acute infection or suspected chronic active infection. Patients with a positive EBV PCR test are excluded.
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or five half-lives of the drug (whichever is longer) 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 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 after principal investigator approval. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab, tiragolumab, oxaliplatin or 5-FU formulation
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months for atezolizumab