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

SRT will be delivered in 3 to 5 treatment fractions over 1 to 2 weeks. Patients will continue
to receive the same FDA-approved PD-1 or PD-L1 inhibitor that they had been receiving at the
time of disease progression until 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.

Inclusion Criteria:

- Pathologically-proven diagnosis of a solid tumor malignancy

- Clinical or radiographic evidence of disease progression during 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.

- Previous tumor response to PD-1 or PD-L1 inhibiting therapy

**Note: Tumor response is defined as CR, PR, or SD that is durable for at least 16
weeks.

- Administration of a PD-1 or PD-L1 inhibitor within 60 days prior to study registration

- For patients who discontinued PD-1 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.

- Determination by the treating radiation oncologist that the patient is a candidate for
SRT

**Note: All brain metastases will receive 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.

- Determination by the treating medical oncologist that the patient is a candidate to
continue the PD-1 or PD-L1 inhibiting therapy that the patient was receiving at the
time of the most recent progression.

- 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.

- Any ≥ grade 3 immune-related adverse events (irAEs) that occurred during previous PD-1
or PD-L1 therapy

- 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.