Dose-escalation Study of Ultra-high Dose Ablative Radiosurgery With Immunotherapy for Bulky Metastatic Cancer Patients

Inclusion Criteria: * Ability of participant to understand this study, and participant willingness to sign a written informed consent * Males and females age ≥ 18 years * Measurable disease by RECIST 1.1 Participants must have at least two radiographically identifiable lesions measurable by RECIST v1.1 criteria and one of those lesions must be ≥65 cc. NOTE: 'cc' equals (width x length x height)/2 to provide rough approximation. For example, a 5.1 x 5.1 x 5.1 cm tumor would be 66.3 cc and appropriate for trial enrollment * Participants must have washout period of 5 elimination half-lives or 28 days (whichever is longer) from time of last systemic therapy to start of study treatment * Women of childbearing potential must have a negative serum pregnancy test at time of enrollment (at screening and up to 48 hours prior to start of radio- or immuno- therapy) * Participants with biopsy and radiographically confirmed metastatic cancer (i.e., Lung, head and neck, ovarian, colorectal, sarcoma) * At least 1st line (1L) systemic therapy or immunotherapy must have failed for participants and standard of care therapy options must also be exhausted. Standard of care options that have been discontinued for reasons other than disease progression are eligible. NOTE: Participants who are off systemic therapy who are being monitored with surveillance imaging, who then develop disease progression and are without standard of care therapy options are eligible for enrollment. * At least one lesion (and up to a maximum of four lesions) must be ≥65 cc (calculated using tumor length x width x height to closest approximation) * Prior RT is permitted if the lesion to be treated and surrounding region (no appreciable dosimetric overlap, assessed on case-by-case basis as needed) with ultra-high dose SBRT was not previously treated * Participants with CNS metastatic disease will be allowed on protocol if all lesions are managed prior to starting extra-CNS ablative therapy * Availability of a representative (FFPE) tumor specimen from metastatic diagnosis of cancer done prior to any study intervention for exploratory study-related biomarker research * Adequate organ function, defined as the following laboratory test results, obtained within 14 days prior to initiation of study treatment: 1. Leukocytes ≥ 3K/µL 2. Lymphocyte count ≥ 0.5 x 10\^9/L (500/µL) 3. Absolute Neutrophil Count ≥1.5K/µL without granulocyte colony-stimulating factor support. NOTE: Participants with established diagnosis of benign neutropenia are eligible to participate with ANC between 1000-1500 if in the opinion of treating physician the trial treatment does not pose excessive risk of infection to the participant 4. Platelets ≥100K/μL) without transfusion 5. Hemoglobin ≥ 9 g/dL 6. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) \[calculated using the Cockcroft-Gault formula\] 7. Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ 1 x ULN. Participants with known Gilbert disease: serum bilirubin ≤ 3 x ULN 8. Serum albumin ≥ 35 g/L (3.5 g/dL) 9. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN 10. For participants not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN 11. For participants receiving therapeutic anticoagulation: stable anticoagulant regimen 12. Negative HIV test at screening, with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/µL, and have an undetectable viral load. \*\*\* NOTE: A participant may be eligible if test is positive and will be left to the investigator to determine appropriateness for trial enrollment if medically stable and without signs of active, uncontrolled disease. Prior to formal enrollment, please contact protocol study PI to review. 13. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test must be performed for participants who have a positive HCV antibody test.\*\*\* NOTE: A participant may be eligible if test is positive and will be left to the investigator to determine appropriateness for trial enrollment if medically stable and without signs of active, uncontrolled disease. Prior to formal enrollment, please contact protocol study PI to review. 14. Negative hepatitis B surface antigen (HbsAg) test at screening. Negative total hepatitis B core antibody (HbcAb) test at screening, or positive total HbcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV DNA test will be performed only for participants who have a negative HbsAg test and a positive total HbcAb test. \*\*\* NOTE: A participant may be eligible if test is positive and will be left to the investigator to determine appropriateness for trial enrollment if medically stable and without signs of active, uncontrolled disease. Prior to formal enrollment, please contact protocol study PI to review. 15. Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section and below for the duration of study participation and for 180 DAYS/6 MONTHS following completion of therapy. Men must refrain from donating sperm during this same period. 1. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. 2. Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. 3. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form. Exclusion Criteria: * Simultaneously enrolled in any therapeutic clinical trial * Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study * Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements * Is pregnant or breastfeeding * Female of childbearing potential planning to become pregnant while receiving study treatment or for less than 180 DAYS/6 MONTHS after the last dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result at time of enrollment (at screening and up to 48 hours prior to start of radio- or immuno- therapy). * Male of childbearing potential planning to father a child or donate sperm while receiving study treatment or for less than 180 DAYS / 6 MONTHS after the last dose of study treatment * Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment * COVID-19: Participants with active COVID-19 symptoms and/or hospitalized for severe or critical COVID-19 symptoms * Participants with uncontrolled concurrent illness or infection (i.e., active pneumonia or infection) * Participants with only bone metastatic disease * Immunosuppressive disorders (i.e., solid organ transplant recipient, allogeneic stem cell transplant) (please refer Appendix D for full list) * Participants who are enrolled in hospice or felt to have less than 6 months life expectation * Uncontrolled or untreated CNS metastases 1. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases 2. Asymptomatic participants with treated CNS lesions are eligible, provided that all of the following criteria are met: 1. Measurable disease, per RECIST v1.1, must be present outside the CNS 2. The participant has no history of intracranial hemorrhage or spinal cord hemorrhage 3. The participant has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment. 4. The participant has no ongoing requirement for corticosteroids as therapy for CNS disease 5. If the participant is receiving anti-convulsant therapy, the dose is considered stable * History of leptomeningeal disease * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). • Participants with indwelling catheters (e.g., PleurX) are allowed. * Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN * Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry. * Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, scleroderma, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: 1. Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study 2. Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study 3. Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: 1. Rash must cover \< 10% of body surface area 2. Disease is well controlled at baseline and requires only low-potency topical corticosteroids 3. There has been 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 4. See also Appendix D for list of autoimmune diseases and immune deficiencies * 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. History of radiation pneumonitis in the radiation field (fibrosis) is permitted * 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 study * 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 participant safety * Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Participants 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 participant at high risk from treatment complications * Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab * Current treatment with anti-viral therapy for HBV * Treatment with investigational therapy within 28 days prior to initiation of study treatment * Prior treatment with checkpoint blockade therapy * History of prior immunotherapy induced pneumonitis and/or peritonitis that is Grade ≥3 is not permitted (instance of Grade 1 or 2 that have fully recovered and tolerated subsequent immunotherapy is permitted) * Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 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-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: 1. Participants 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 2. Participants 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 * Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation * Known allergy or hypersensitivity to any component of the atezolizumab formulation * Has a known allergic reaction to any excipient contained in the study drug formulation