Immune Checkpoint Inhibitor and MR-guided SBRT for Limited Progressive Metastatic Carcinoma.

Inclusion Criteria:

1. 18 years of age at the time of study entry.
2. Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
3. Life expectancy of .12 weeks as estimated by the treating physician.
4. Metastatic carcinoma confirmed by biopsy or imaging study if biopsy is not deemed feasible.
5. Most recent anti-cancer therapy consists of a single ICI drug including but not limited to ipilimumab, nivolumab, pembrolizumab, atezolizumab.
6. Radiographic evidence of progression while on a single ICI drug in 1 and up to 5 lesions.
7. Eligible to continue ICI during and after radiation therapy.
8. 3 radiographically distinct and measurable lesions (primary and/or metastatic lesions) by RECIST 1.1 criteria, with .3 lesions separated from each other by .5 cm
9. Subjects must consent to all study procedures described in the protocol including radiographic evaluation and blood draws.
10. Immunosuppressive doses of systemic medication including steroids must be discontinued at least 14 days prior to the start of radiation therapy.
11. Adequate normal organ and marrow function
12. Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: .60 years old and no menses for .1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy), have a negative serum pregnancy test within 14 days of study enrollment, and not be breastfeeding.

Exclusion Criteria:

1. Any contraindication to having an MRI scan.
2. Chemotherapy, biologic agent, investigational therapy, or radiation therapy given within 14 days of study enrollment.
3. Symptomatic or uncontrolled brain metastasis requiring treatment.
4. The need for palliative radiation therapy to a non-target lesion prior to radiation therapy to one of 2 target lesion on this study.
5. Prior radiation therapy to any lesion that would receive radiation therapy on this protocol.
6. Prior radiation therapy to a lesion located within 4 cm of previously irradiated structures: spinal cord that previously received >45 Gy; brachial plexus that previously received >45 Gy; small/large intestine or stomach that previously received >45 Gy; prior total lung V20 >30%.
7. Prior radiation therapy that could lead to an unacceptably high risk of clinically significant normal tissue injury due to high cumulative normal tissue dose as determined by the investigator.

8. History of any primary malignancy with the exception of

   1. Malignancy treated with curative intent and with no known active disease for at least 3 years before enrollment on this study.
   2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
   3. Adequately treated carcinoma in situ without evidence of disease (i.e. cervical carcinoma in situ; superficial bladder cancer).
9. Any unresolved toxicity (Common Terminology Criteria for Adverse Events version 5.0 > grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to worsen by treatment on this study are permitted to enroll on this study.
10. Active or prior documented autoimmune disease within the past 2 years. Subjects with vitiligo, type I diabetes mellitus, Graves disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
11. Subjects requiring systemic corticosteroid (>10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days of study enrollment.
12. Contraindication to IV contrast despite premedication for iodine allergy, which would limit the ability to assess radiographic response to study treatment.
13. Prior allogeneic organ transplantation.