SBRT + PD-1/PDL-1 Inhibiting Therapy for Advanced Solid Tumors After Dz Control on PD-1/PDL-1 Tx

The purpose of this study is to find out if having radiation therapy and continuing immunotherapy can improve the benefit of immunotherapy. There have been reports of patients who were treated with radiation therapy that not only caused the treated tumors to shrink or stop growing, but also resulted in tumors that had not been treated in other parts of the body to shrink or stop growing. This effect is thought to be brought about by cells in the body's immune system that become active as a result of the effects of radiation therapy. If radiation therapy can stimulate the immune system, it may be possible for immunotherapy to be helpful again in treating a cancer that the immunotherapy drug helped treat before. This study will also check if receiving immunotherapy at the end of radiation therapy has any effect on the side effects of radiation therapy or immunotherapy.

Stereotactic radiotherapy (SRT) will be delivered in up to 10 treatment fractions over 1 to 2 weeks. Patients will continue to receive the same FDA-approved programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor that they had been receiving at the time of disease progression through 52 weeks following completion of SRT.

Correlative blood samples will be collected at baseline, prior to the second SRT fraction, after the last SRT fraction (on the same day), and at 8, 24, and 52 weeks after the last SRT fraction. These samples will be used to determine the mechanistic immunologic effects of therapy.

Eligibility Criteria:
Inclusion Criteria:

* Pathologically-proven diagnosis of a solid tumor malignancy
* One of the following criteria must be met:
* Clinical or radiographic evidence of disease control (defined as best response of stable disease (SD) or partial response (PR) or combination of both for ≥ 16 weeks) without evidence of complete response (CR) or progression OR
* Clinical or radiographic evidence of disease progression during treatment with PD-1 or PD-L1 inhibiting therapy, following previous tumor response (CR, PR, or SD for ≥ 16 weeks) to PD-1 or PD-L1 inhibiting therapy, and, for patients who discontinued PD-1 or PD-L1 inhibiting therapy during response to therapy, disease progression must have occurred following at least 8 weeks of re-treatment with PD-1 or PD-L1 inhibiting therapy Note: Both the treating medical oncologist and radiation oncologist must be in agreement with determination of disease progression.
* Administration of a PD-1 or PD-L1 inhibitor within 60 days prior to study registration
* Determination by the treating radiation oncologist that the patient is a candidate for SRT (ie, radiation therapy with a stereotactic setup) Note: All brain metastases will receive stereotactic radiotherapy (SRT).
* The total number of tumors requiring SRT must be ≤ 5 Note: Regardless of the number of brain metastases that will be treated with SRT, the brain metastases will be considered to be one tumor.
* Measurable disease by RECIST v1.1 that will not undergo SRT and that is amenable to monitoring Note: all brain metastases will receive SRT. Therefore, a patient with brain metastases that will be treated with SRT must also have extracranial disease that will not undergo SRT and that is amenable to monitoring
* Determination by the treating medical oncologist that the patient is a candidate to continue the PD-1 or PD-L1 inhibiting therapy that had previously provided disease control
* Age ≥ 18 years
* Karnofsky Performance Status score of ≥ 60 %
* A woman of childbearing potential (WCBP), defined as a woman who is \< 60 years of age and has not had a hysterectomy, must have a documented negative serum pregnancy test within 14 days prior to initiating study treatment
* Ability to understand and willingness to sign the consent form

Exclusion Criteria:

* Other anti-cancer therapy administered between the time of tumor response to PD-1 or PD-L1 therapy and time of study enrollment Note: Patients treated with a combination of PD-1 or PD-L1 inhibiting therapy and other immunotherapy are eligible; patients taking hormonal anti-cancer therapies or steroids for central nervous system (CNS) edema management that, in the opinion of the investigator, are appropriate to continue are eligible.
* Any prior PD-1/PD-L1 therapy-related AE that, in the opinion of the investigator, warrants exclusion from participation in this trial
* Administration of any investigational agent within 4 weeks prior to initiating study treatment
* Known active hepatitis B or C
* Pregnancy or breastfeeding
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements