Concurrent Immunotherapy and Systemic Therapy With Stereotactic Body Radiation Therapy (SBRT) for Stage IV Cancers (COINSSS IV)

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to 99 Years
• SexAll
• Healthy volunteersNo

You may be able to join if

• Histologically proven advanced or stage IV head & neck, non-small cell lung cancer, cervical, esophageal, gastric, and gastroesophageal cancer at least 6 metastases that are eligible for SBRT comprising: lung, liver, adrenal glands, bone, and lymph node sites with at least 1 other lesion meeting RECIST criteria of which this additional lesion not be treated with SBRT (biopsies performed for diagnosis are standard of care).
• At least 6 metastases eligible for SBRT comprising: lung, liver, adrenal glands, bone, and lymph node sites
• The 1 irradiated lesion must have a max point dose of 5Gy or less.
• Eligible for Immunotherapy for an FDA-approved indication as defined in section 6.1. NOTE: No limit is placed on prior systemic treatment unless it affects the eligibility for administration of immune checkpoint inhibitor therapy.
• If prior treatment with chemotherapy or radiotherapy or surgery has occurred: Prior chemotherapy or radiation must have concluded > 21 days prior to the start of study treatment. Exception: study treatment can start within 2-3 days following GKS [gamma knife surgery] or whole brain radiation therapy [ WBRT], as long as patient is not experiencing ongoing/residual AE's related to GKS or WBRT at discretion of treating physician.
• First Line immunotherapy-based treatments only. The patient may have received prior cycles of immunotherapy, but has to be on the first line of immunotherapy-based treatments.
• If non-small cell lung cancer patient with pembrolizumab, PD-L1 testing CPS score > or = to 50% will have to be shown
• If cervical cancer patient on secondary line therapy with pembrolizumab, CPS score of > or = to 1 will have to be done. Please note, second line therapy with pembrolizumab is only allowed if the patient's first line of therapy did NOT include immunotherapy.
• If non-small cell lung cancer on first line ipilimumab in combination with nivolumab, PD-L1 of 1% and negative epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
• If pembrolizumab is given for a gastric cancer, a PD-L1 expression (CPS =1) will need to be shown
• If pembrolizumab is given as a single agent treatment after progression of one prior systemic therapy agent for esophageal or gastroesophageal squamous cell carcinoma histology, a PD-L1 (CPS=1) expression will have to be shown.
• ECOG Performance Status 0 - 1 (see Appendix A).
• Life expectancy > or equal to 6 months.
• Adequate organ and bone marrow function prior to study treatment as defined by: Thresholds for lab values prior to initiation of study treatment.
• ANC > or equal to 1,000/mm3
• Platelets > or equal to 100,000/mm3
• Total bilirubin < or equal to or equal to 1.5 x ULN
• AST and ALT - With hepatic metastasis, < or equal to or equal to 5 x ULN. If no hepatic metastasis, < or equal to 2.5 times x ULN
• Creatinine Or Creatinine Clearance < or equal to 1.5 x ULNand/or CrCl > or equal to 30ml/min (per 24-hour urine collection) or calculated according to the Cockcroft-Gault formula (Appendix B)
• No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for the past 3 years.
• Non-pregnant and non-nursing women -Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
• Women of childbearing potential and men must agree to use adequate contraception methods prescribed their the patients primary care physician, urologist, or obstetrician/gynecologist prior to study entry and for the duration of study participation.
• Subjects should use adequate birth control for at least 3 months after the last administration of immune checkpoint inhibitors.
• Ability to understand and the willingness to sign a written informed consent document

You cannot join if

• Presence of < or equal to 5 sites amenable to SBRT
• Ineligible for immune checkpoint inhibitors based on package insert of the chosen immune checkpoint inhibitor
• No more than 7 metastatic sites to an organ, defined as liver, left lung, right lung, single anatomically bone site (e.g. femur, humerus, single vertebral body).
• NOTE: Multiple different vertebral bodies are allowed.
• Peritoneal involvement, at the discretion of the study PI. NOTE: Peritoneal metastasis does not exclude GI nor cervical cancer, except in cases where there is a separate focus of spread to the peritoneum.
• Presence of liver cirrhosis of any grade prohibits SBRT to the liver. NOTE: Pt can enroll to trial if receiving SBRT to other non-liver metastatic sites.
• A plan that cannot meet organ at risk tolerance (as defined in section 6.7.2.1) Auto-immune diagnosis Medications prohibited while receiving concurrent SBRT: gemcitabine, Adriamycin, VEGF or BRAF inhibitors.
• NOTE: However, if the patient is on the prohibited agent(s), the patient is still eligible for the trial so long as the prohibited agent can safely be held for at least 1 month before starting SBRT, during SBRT, and 1 month after completion of SBRT.
• Major surgical procedure (including craniotomy and open brain biopsy) or significant traumatic injury (injury requiring immediate surgical intervention or involving loss of consciousness) within 14 days prior to registration or those patients who receive a nonCNS minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 3 days prior to registration.
• NOTE: There is no waiting period for central line placement. There is a 7-day window for recovery prior to registration for patients who underwent stereotactic biopsy of the brain.
• Active clinically serious infection > CTCAE Grade 2.
• Serious non-healing wound, ulcer or bone fracture.
• Uncontrolled inter-current illness. This includes, but is not limited to: ongoing or active infection; symptomatic congestive heart failure (NYHA class III or IV); unstable angina pectoris or new onset angina that began within the last 3 months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; thrombotic/ embolic events such as cerebrovascular accident, including transient ischemic attacks within the past 6 months;
• Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management; Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C; Known Grade 3 or 4 neurotoxicity.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of ICI.
• Note: Patients, if randomized, should not receive live vaccine while receiving ICI and up to 30 days after the last dose of ICI.
• Inclusion of Women and Minorities - Consistent with NIH policy, both men and women of all races and ethnic groups are eligible for this trial.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

pembrolizumab. A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity. NCI Drug Dictionary

nivolumab. A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity. NCI Drug Dictionary

atezolizumab. A humanized, Fc optimized, monoclonal antibody directed against the protein ligand PD-L1 (programmed cell death-1 ligand 1; CD274), with potential immune checkpoint inhibitory and antineoplastic activities. Atezolizumab binds to PD-L1, blocking its binding to and activation of its receptor programmed death 1 (PD-1; PDCD1) expressed on activated T cells, which may enhance the T-cell-mediated immune response to neoplasms and reverse T-cell inactivation. In addition, by binding to PD-L1, atezolizumab also prevents binding of this ligand to B7.1 (CD80) expressed on activated T cells, which further enhances the T-cell-mediated immune response. PD-L1 is overexpressed on many human cancer cell types and on various tumor-infiltrating immune cells. PD-L1 binding to PD-1 on T cells suppresses the immune system and results in increased immune evasion. PD-1, a transmembrane protein, is a negative regulator of the immune system that limits the expansion and survival of CD8+ T cells. The Fc region of atezolizumab is modified in such a way that it does not induce either antibody-dependent cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). NCI Drug Dictionary

ipilimumab. A recombinant human immunoglobulin (Ig) G1 monoclonal antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), with immune checkpoint inhibitory and antineoplastic activities. Ipilimumab binds to CTLA4 expressed on T cells and inhibits the CTLA4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system. NCI Drug Dictionary

Treatments listed in the registry

• Stereotactic Body Radiation Therapy (SBRT) (Radiation): SBRT administered to 6-10 metastatic lesions during the first cycle of immunotherapy.
• Pembrolizumab (Drug): FDA-approved immune checkpoint inhibitor administered according to standard clinical practice and disease-specific indications.
• Nivolumab (Drug): FDA-approved immune checkpoint inhibitor administered according to standard clinical practice and disease-specific indications.
• Atezolizumab (Drug): FDA-approved immune checkpoint inhibitor administered according to clinical practice and disease-specific indications.
• Ipilimumab (Drug): FDA-approved immune checkpoint inhibitor administered according to standard clinical practice and disease-specific indications.

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• radiation: Part of the study plan

Main goals

• 6-Month Progression-Free Survival (PFS) (6 Months)

Other goals

• Acute Grade 2 or Higher Toxicity
• Overall Survival
• Local Recurrence-Free Survival
• Distant Metastasis Progression-Free Survival
• Objective Response Rate
• Continuation of Systemic Therapy

Planned enrollment: 35 (estimated).

• University of Kentucky Markey Cancer Center, Lexington, Kentucky

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07770100
• NCI Drug Dictionary: C106432
• NCI Drug Dictionary: C68814
• NCI Drug Dictionary: C106250
• NCI Drug Dictionary: C2654

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 13, 2026. Public record; not medical advice.