A Phase II Study of Immunotherapies (Tiragolumab and Atezolizumab) in Combination With Stereotactic Body Radiation Radiotherapy in Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)
Background: Metastatic colorectal cancer (mCRC) is cancer that has spread beyond the colon and rectum. Most people with mCRC die within 5 years. New immune-based treatments are making progress with some types of colon cancer. But these treatments do little for people with a type of cancer that is microsatellite stable (MSS). MSS is a specific cancer biomarker. Better treatments are needed.
Objective: To test 2 drugs (tiragolumab and atezolizumab) combined with radiation therapy in people with MSS mCRC.
Eligibility: People aged 18 years and older with MSS mCRC.
Design: Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and a test of their heart function. They will provide a tissue sample from their tumor; if one is not already available, a new sample will be taken. Their ability to perform normal tasks will be assessed. Tiragolumab and atezolizumab are both administered through a tube attached to a needle inserted into a vein. Participants will receive both drugs on day 1 of 3-week treatment cycles. Each study visit should last about 8 hours. Participants will receive radiation therapy on days 1, 3, and 5 of cycle 1 only. Blood samples and rectal swabs will be collected on day 1 of every cycle. Imaging scans will be repeated every 9 weeks. Additional tumor samples may be taken during treatment. Treatment will continue for up to 2 years. Participants will have a follow-up visit 1 month after treatment ends. Follow-up visits will continue every 3 months for 1 more year.
• Histologically or cytologically confirmed colorectal cancer (CRC) by the NCI Laboratory of Pathology (LP). Note: Participants must provide tumor sample or be willing to undergo biopsy to confirm the diagnosis.
• Evidence of metastatic involvement.
• History of microsatellite stable (MSS) status.
• Age \>= 18 years.
• Weight \> 35 kg.
• ECOG performance status \<= 1
• Must have measurable disease, per RECIST 1.1
• At least 2 lesions present, one of which must be amenable to SBRT and second lesion outside the radiation field must serve as target lesion to evaluate measurable disease.
• Must have progression of disease, been treated or intolerant to at least 2 lines of systemic standard of care treatment in the metastatic setting (e.g., fluoropyrimidine-, oxaliplatin-, or irinotecan-based therapy \[unless ineligible for any of these drugs\]).
• Participants with a history of RAS wild-type tumor must have progressed, been intolerant of OR refused anti-EGFR based treatment.
• Participants must have adequate organ and marrow function as defined below:
‣ Leukocytes \>= 3,000/microL
⁃ Absolute neutrophil count \>= 1,500/microL
⁃ Lymphocyte count \> 500/microL
⁃ Platelets \>= 100,000/microL without transfusion or at least \> 48 hours post-completion of blood transfusion
⁃ Hemoglobin \>= 9 g/dL without transfusion or at least \> 48 hours post-completion of blood transfusion
⁃ International normalized ratio \<=1.5 x institutional upper limit of normal
⁃ (INR) and partial thromboplastin time (aPTT) (ULN) (if not receiving therapeutic anticoagulation)
⁃ Serum albumin \> 2.5 g/dL
⁃ Total bilirubin \<= 1.5 x ULN
⁃ Aspartate aminotransferase (AST) \<= 2.5 x institutional ULN
⁃ Alanine transaminase (ALT) \<= 2.5 x institutional ULN
⁃ Alkaline phosphatase (ALP) \<= 2.5 x institutional ULN
⁃ Creatinine clearance calculated by Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) equation \>= 50 mL/min/1.73 m\^2 for participants with creatinine levels \>= 1.5 mg/dL
• Participants receiving therapeutic anticoagulation must be on an established, stable anticoagulation regimen prior to starting the study therapy.
• Negative human immunodeficiency virus (HIV) serological testing at screening.
• Participants seropositive for hepatitis B virus (HBV) antibody test are eligible if at screening:
‣ have a negative HBV DNA test and
⁃ not on treatment with anti-viral therapy for HBV.
• Participants seropositive for hepatitis C virus (HCV) antibody test, are eligible if have a negative HCV RNA test at screening.
• Participants seropositive for Epstein-Barr virus (EBV) viral capsid antigen immunoglobulin M (IgM) test are eligible if have a negative EBV polymerase chain reaction (PCR) test at screening.
• Participants must have recovered from prior toxicity or adverse events to grade \<= 2 per Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.
• Women of child-bearing potential (WOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device \[IUD\], surgical sterilization, abstinence) at the study entry and up to 5 months after the last dose of the study drugs (restriction period).
∙ Note: A woman is considered to be of child-bearing 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 (i.e., removal of ovaries, fallopian tubes, and/or uterus).
• Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 5 months after the last dose of the study drugs.
• Participants must be willing to co-enroll in protocol 11-C-0112, Acquisition of Blood and Tumor Tissue Samples from Patients with Gastrointestinal Cancer .
• Participants must understand and be willing to sign a written informed consent document.