Table 5.

Currently ongoing clinical trials.

Study Identifier	Study Title	Status	Condition or Disease	Therapy	RT Scheme	Cohort N	Planned Primary Outcome Measures	Planned Secondary Outcome Measures
NCT03480334	Abscopal Effect of Radiotherapy and Nivolumab in Relapsed Hodgkin Lymphoma After Anti-PD-1 Therapy (AERN)	Recruiting	Classical Hodgkin lymphoma	Nivolumab + RT	20 Gy	29	Abscopal response rate	-
NCT03396471	Study of Pembrolizumab and Concurrent Radiation in Patients With Previously Treated Carcinoma of Unknown Primary	Recruiting	Carcinoma, unspecified site	Pembrolizumab + EBRT	20-30 Gy, 5 fr	34	Abscopal response rate	Response rate
								Assess adverse events
								Progression free survival
								Overall survival
								Time-to-progression
								Disease control rate
NCT04238169	Clinical Trial Assessing the Efficacy of Abscopal Effect Induced by SBRT and Immunotherapy in Advanced NSCLC	Recruiting	Non-Small-Cell Lung Cancer (NSCLC)	(Bevacizumab +) Toripalimab + SBRT	30-50 Gy, 5 fr	60	Objective response rate	Progression free survival
								Duration of response
							Objective response of non-target lesion	Overall survival
								Incidence of adverse events
								Quality of life
NCT04873440	An Open-label, Phase I/II Study of Manganese Plus Radiotherapy in Patients With Metastatic Solid Tumors or Lymphoma	Recruiting	Solid tumor	Manganese Chloride + RT (Chemo-immuno-therapy)	standard-of-care RT or SBRT to one metastatic site	10	Proportion of subjects with an abscopal response	Disease control rate
								Progression free survival
			Lymphoma				Number of treatment-related adverse events	Overall survival
								Number of participants with laboratory test abnormalities
NCT04168320	SBRT-based PArtial Tumor Irradiation of HYpoxic Segment (SBRT-PATHY)	Recruiting	Unresectable malignant solid neoplasm bulky tumors	SBRT	SBRT-based PArtial Tumor irradiation targeting HYpoxic segment	30	Bystander and abscopal effects	Overall survival
								Progression free survival
								Patient-reported outcome
								Incidence of adverse events
								Response evaluation criteria in solid tumors
								Timing
NCT03449238	Pembrolizumab And Stereotactic Radiosurgery (Srs) Of Selected Brain Metastases In Breast Cancer Patients	Recruiting	Metastatic breast cancer	Pembrolizumab + Stereotactic Radiosurgery	n/a	41	Tumor response for non-irradiated brain lesions	Number of participants with abscopal response
			Brain metastases				Correlation of abscopal responses with the radiation dose received
							Overall survival
NCT04245514	Multimodality Treatment in Stage III Non-small Cell Lung Cancer (NSCLC)	Recruiting	Non-Small-Cell Lung Cancer (NSCLC)	Durvalumab + RT	40 Gy, 20 fr	90	Event-free survival	Recurrence-free survival after resection
								Overall survival
					25 Gy, 5 fr			Objective response
								Pathological complete response
					24 Gy, 3 fr			Major pathological response
								Complete resection
NCT04530708	Addition of Radiotherapy to Standard Medical Treatment for Stage IV NSCLC (MARS)	Recruiting	Non-Small-Cell Lung Cancer (NSCLC)	Thoracic RT vs. standard of care	36 Gy	162	Difference in quality of life	Overall survival
								Progression free survival
								Toxicity of esophagitis, pneumonitis, dyspnea, fatigue, cough
NCT04212026	Irreversible Electroporation (IRE) Followed by Nivolumab in Patients With Metastatic Pancreatic Cancer.	Recruiting	Metastatic pancreatic cancer	Nivolumab	n/a	15	Overall response rate (ORR) of the reference liver metastasis	ORR of primary tumor site (pancreas)
								ORR of IRE-treated liver metastasis
								Progression free survival (PFS)
								Overall survival
								Adverse events
NCT03474497	IL-2, Radiotherapy, and Pembrolizumab in Patients Refractory to Checkpoint Blockade	Recruiting	NSCLC, Head and neck squamous cell carcinoma,	IL-2 + Pembrolizumab + RT	24 Gy, 3 fr, palliative regimen	45	Abscopal response rate	Maximum tolerated dose
			Metastatic melanoma
			Metastatic RCC
NCT03548428	Stereotaxic Body Irradiation of Oligometastase in Sarcoma (Stereosarc)	Recruiting	Sarcoma	Atezolizumab + SBRT	3 to 5 fr depending on tumor size	103	Progression-free survival (PFS) rate	PFS by immune response criteria
								Ratio PFS after RT/PFS during previous treatment
								Objective response rate
								Toxicity of treatment
								Overall survival
								Quality of life
								Evaluation of the cost of treatment
								Rate of PET-CT at inclusion
								Impact of biomarkers on PFS or response rate
								Developing mathematical models
NCT03927898	Phase II Study of Toripalimab Plus Stereotactic Body Radiotherapy in Colorectal Cancer Patients With Oligometastasis	Recruiting	Metastatic colorectal cancer	Toripalimab + SBRT	SBRT (BED >80Gy) to oligometastatic lesions	40	1 year progression free survival (PFS)	Acute adverse events
								Objective response rate
								2 year local control rate
								2 year overall survival
								T cell receptor repertoire/T cell clones in blood
								Expression of PD-1, Ki-67 on T cell
								Expression of PD-L1 on exosomes in blood
								Expression of PD-L1 on circulation tumor cell
NCT03774732	PD-1 Inhibitors and Chemotherapy With Concurrent Irradiation at Varied Tumour Sites in Advanced Non-small Cell Lung Cancer (NIRVANA-LUNG)	Recruiting	Non-Small-Cell Lung Cancer (NSCLC)	Pembrolizumab + Chemotherapy + Radiotherapy	at least 18 Gy in 3 fr	460	Overall survival	Tumour response
								Progression free survival
								Local and distant controls in irradiated patients
				Pembrolizumab + Chemotherapy				Quality of life
								Acute/late toxicities
NCT04299646	Study Assessing Stereotactic Radiotherapy in Therapeutic Strategy of Oligoprogressive Renal Cell Carcinoma Metastases (GETUG-StORM-01)	Recruiting	Metastatic RCC	Stereotactic RT + systemic treatment	n/a	114	Progression free survival	Treatment-related adverse events
								Local control rate
								Overall control rate
NCT03316872	Study of Pembrolizumab and Radiotherapy in Liver Cancer	Recruiting	Hepatocellular carcinoma	Pembrolizumab + SBRT	n/a	30	Overall response rate	Response rate in non-irradiated tumor lesions
								Progression free survival rate
								Overall survival rate
NCT03277482	Durvalumab, Tremelimumab + Radiotherapy in Gynecologic Cancer	Recruiting	Recurrent gyneco-logical cancer	Durvalumab + Tremelimumab + RT	n/a	32	Maximum tolerated dose	Overall response rate
			Metastatic cervical cancer					Local response rate
			Metastatic ovarian cancer					Abscopal response rate
			Metastatic vaginal cancer					Response duration
			Metastatic vulvar cancer					Progression free survival
			Metastatic endometrial cancer
NCT03085719	Targeting PD-1 Therapy Resistance With Focused High or High and Low Dose Radiation in SCCHN	Recruiting	Head and neck cancer	High dose radiation + Pembrolizumab	n/a	26	Overall response rate	Overall survival
								Progression free survival
								Treatment-related adverse events
								Immune-related response
								Local response
								Clinical benefit rate
								Abscopal response
NCT03176173	Radical-Dose Image Guided Radiation Therapy in Treating Patients With Metastatic Non-small Cell Lung Cancer Undergoing Immunotherapy	Recruiting	Non-Small-Cell Lung Cancer (NSCLC)	Immunotherapy + Image Guided RT	n/a	85	Progression free survival	Change in ctDNA levels
								Immune marker levels from peripheral blood
								Acute and late toxicity
								Overall survival
								Patterns of response and progression
								Time to discontinuation of study
NCT04221893	Radiation Therapy for the Treatment of Metastatic Gastrointestinal Cancers	Recruiting	Esophageal adenocarcinoma	RT	n/a	28	Overall response rate	Progression free survival
			Esophageal squamous cell carcinoma					Overall survival Determine local control in radiated lesion(s)
			Gastric cancer					Tumor measurement change
			Adenocarcinoma of gastroesophageal junction					New metastatic lesions Adverse events
NCT03385226	A Trial Assessing the Effect of Pembrolizumab Combined With Radiotherapy in Patients With Relapsed, Refractory, Specified Stages of Cutaneous T-cell Lymphoma (CTCL) Mycosis Fungoides (MF)/Sezary Syndrome (SS) (PORT)	Recruiting	Cutaneous T cell lymphoma	Pembrolizumab + RT	12 Gy, 3 fr	46	Overall response (global assessment)	Response and duration
								Safety and toxicity
								Progression free survival
								Overall survival
								Abscopal effect rate
								Changes in immune status
								Plasma HMGB-1 levels
								Functional analysis of isolated cell populations
								Assessment of diversity and clonality of T cells
								Immune signatures for responders and non-responders
								Tumor-infiltrating lymphocyte-specific neo-antigens
								Expression of immunological checkpoints
								Investigation of tumor immune microenvironment
NCT02858869	Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases	Recruiting	Metastatic malignant	Pembrolizumab + Stereotactic Radiosurgery	SRS 6 Gy, 9 Gy or 18–21 Gy	30	Proportion of dose-limiting toxicities	Absolute cell counts for pre and post-treatment serum immune biomarkers
			Neoplasm in the brain
			Metastatic melanoma					Overall response
			Mucosal melanoma					Overall survival
			Ocular melanoma					Rate of anywhere intra-cranial failure
			Non-Small Cell Lung Cancer					Rate of leptomeningeal disease
			Skin melanoma					Rate of local recurrence
			Melanoma of unknown primary					Rate of symptomatic radiation necrosis
NCT02830594	Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer	Active, not recruiting	Gastric and esophageal adeno-carcinoma	EBRT + Pembrolizumab	n/a	14	Tumor-infiltrating cytotoxic T cells and circulating cytotoxic T cells	Incidence of adverse events
			Gastric and esophageal squamous cell carcinoma				Immunosuppressive Tregs in non-irradiated sites	Overall response rate
			Gastroesophageal junction adeno-carcinoma				MDSCs in non-irradiated sites	Progression free survival
			Metastatic malignant neoplasm in the stomach					Overall survival
NCT03469713	Nivolumab Plus Stereotactic Body Radiotherapy in II and III Line of Patients With Metastatic Renal Cell Carcinoma (NIVES)	Active, not recruiting	Metastatic renal cancer	Nivolumab + SBRT	30 Gy in 3 consecutive fractions	69	Objective response rate (ORR)	Progression free survival
								Overall survival
								ORR of irradiated and non-irradiated metastases and duration of response
								Incidence, nature and severity of adverse event
								Analysis of expression of PD-L1
								Analysis of the genetic background of tumor
								Analysis of the immuno-modulation
								Identification of somatic mutations associated with acquired resistance to checkpoint inhibitors
NCT03453892	Investigation of the Timely-coordinated Therapy of Patients With Metastatic Cancer by Radiotherapy Together With Immune Checkpoint Inhibition (ST-ICI)	Active, not recruiting	Metastatic cancer	RT + Ipilimumab	n/a	150	Systemic and local response of detected metastases	Detection of adverse events
								Documentation of corticoid prescription
				Nivolumab + Pembrolizumab + RT			Change of circulating immune cells by deep immunophenotyping	Overall survival
								Progression free survival
NCT03322384	Phase I/II Trial of Epacadostat, Intralesional SD101, Radiotherapy in Patients With Lymphoma	Active, not recruiting	Advanced solid tumors	Epacadostat + SD-101 + RT	24 Gy, 3 fr	20	Maximum tolerated dose	Abscopal response rate
			Lymphoma		20 Gy, 5 fr		Oncidence of treatment-emergent adverse events
NCT03539198	Study of Proton SBRT and Immunotherapy for Recurrent/Progressive Locoregional or Metastatic Head and Neck Cancer	Active, not recruiting	Head and neck cancer	Proton SBRT + Nivolumab	35–45 Gy, 5 fr	91	Objective response rate	Local control rate, overall survival
								Progression free survival
								Time to progression
								New development of distant metastasis
								Quality of Life
								Predictive and prognostic biomarker
NCT03042156	Immunotherapy And Palliative Radiotherapy Combined In Patients With Advanced Malignancy	Active, not recruiting	Advanced cancer	Palliative RT	n/a	30	Number of patients showing toxicity	In-field response on imaging and evidence of out of field (abscopal) response
								Biomarkers analyses as indicator of abscopal response
								Patient-reported outcome
								Inflammatory and radiation sensitivity signatures
NCT03483012	Atezolizumab + Stereotactic Radiation in Triple-negative Breast Cancer and Brain Metastasis	Active, not recruiting	Breast cancer	Atezolizumab + stereotactic radiosurgery (SRS)	n/a	45	Progression free survival	Extracranial objective response rate
								Abscopal response rate
								Clinical benefit rate
								Overall survival
								Patient-reported outcome
								Development of radiation necrosis
								Assessed neurological evaluation
								Dose-limiting toxicity
NCT02888743	Durvalumab and Tremelimumab With or Without High or Low-Dose Radiation Therapy in Treating Patients With Metastatic Colorectal or Non-small Cell Lung Cancer	Active, not recruiting	Metastatic colorectal	Tremelimumab + Durvalumab	n/a	180	Overall response rate	Progression free survival
								Overall survival
								Objective response
			Carcinoma metastatic lung					Incidence of adverse events
				Tremelimumab + Durvalumab + RT				Local control rate and abscopal response rates
			Non-Small Cell Carcinoma					Prognostic effect of PD-L1 expression
								Prognostic effect of T-cell infiltration
								Symptomatic adverse events
NCT02587455	Pembrolizumab and Palliative Radiotherapy in Lung (PEAR)	Active, not recruiting	Thoracic tumours	Pembrolizumab + RT	n/a	48	Toxicity rate	Progression free survival rates
								Overall survival rates
								Duration of clinical benefit
							Maximum tolerated dose	Response rates
								Assessing individual lesion response
								Identify biomarkers and correlate with clinical benefit
NCT03601455	Radiation Therapy and Durvalumab With or Without Tremelimumab in Treating Participants With Unresectable, Locally Advanced, or Metastatic Bladder Cancer	Active, not recruiting	Bladder urothelial carcinoma	RT + Durvalumab	n/a	13	Incidence of adverse events	Local control at primary irradiate site
								Pathologic complete rate of irradiated tumor
								Overall response rate
								Abscopal response
								Duration of response
								Disease-specific survival
				RT + Durvalumab + Tremelimumab			Progression free survival	Overall survival
								Incidence of adverse events
								Immune cell subsets and PD-L1 in tumor biopsies
								Gene signature biomarker
								Circulating immune cell subsets
								Circulating and tumor-infiltrating T-cell receptor repertoire

Abbreviations: RT: radiotherapy; NSCLC: Non-Small-Cell Lung Cancer; fr: fractions; SBRT: stereotactic body radiotherapy; n/a: not available; ORR: overall response rate; IRE: irreversible electroporation; PFS: progression free survival; RCC: renal cell carcinoma; PET-CT: positron emission tomography; CT: computed tomography; BED: radiation biologically effective dose; PD-1: programmed cell death protein 1; PD-L1: PD-1 receptor-ligand 1; ctDNA: circulating tumor DNA; HMGB1: high-mobility group box 1; SRS: stereotactic radiosurgery.