Table 2.

Trials testing radiotherapy in combination with PD-1/PD-L1 in advanced metastatic cancers that allowed more than one irradiated lesions.

NCT number	Phase	Tumor type	RT regimen	PD-1/PD-L1 inhibitors	Treatment schedule timing	Numbers of irradiated targets	Trial design (arms)	Primary outcome	Status
NCT03464942	II	Advanced triple negative breast cancer	SABR 20 Gy × 1f or 8 Gy × 3f	Atezolizumab	PD-1 inhibitor will be started within 5 days of last SABR dose	1–4 metastases with at least 1 untreated	Arm A:Single Dose Arm B:Fractionated Dose	PFS	Recruiting
NCT03283605	I/II	Metastatic head and neck carcinomas	Not mentioned	Durvalumab Tremelimumab	SBRT will be administered between Cycle 2 and 3 of durvalumab and tremelimumab	2–5	Single group	AE PFS	Recruiting (64)
NCT03644823	II	Advanced NSCLC	6 Gy × 3f	Atezolizumab	Not mentioned	1–2	Single group	AE	Recruiting
NCT03812549	I	Stage IV NSCLC	SBRT 10 Gy × 3f	Sintilimab	Sintilimab will be started within 7 days after radiation completed	At least 2	Single group	AE and/or DLT	Recruiting
NCT04549428	II	Advanced oligoprogressive NSCLC	8 Gy × 1f	Atezolizumab	RT will be delivered concomitant to the 2nd dose of atezolizumab	All eligible metastatic and primary sites	Single group	ORR	Not yet recruiting
NCT04625894	I	Oligometastatic gastrointestinal cancer	Multisite SABR (BED > 100 Gy)	Camrelizumab	SABR prior to PD-1 inhibitor	Multisite	Single group	DLT	Not yet recruiting
NCT02303366	I	Oligometastatic breast neoplasia	20 Gy × 1f	MK-3475	SABT followed by MK-3475	At least one metastases (to a maximum of five metastases)	Single group	Safety profile	Completed
NCT03223155	I	Metastatic lung cancer	Three or five fractions of radiation	Nivolumab	Sequential Arm: nivolumab/ipilimumab between 1 and 7 days after completion of SBRT. Concurrent Arm: nivolumab/ipilimumab first and must complete planned SBRT to 2–4 sites within 2 weeks	2–4	Sequential Arm Concurrent Arm	AE	Recruiting
NCT03087019	II	Recurrent or metastatic ACC	>5 fractions	Pembrolizumab	Concurrent	Up to 5	Arm A: Pembrolizumab + Radiation Arm B: Pembrolizumab	ORR	Active, not recruiting
NCT04535024	II	MSS oligometastatic colorectal cancer	Target dose will be adjusted depending on site of the lesion and organs at risk (BED > 100 Gy).	Sintilimab	Starts within 1 week upon SABR completion	Sequence of irradiation for multiple metastases	Single group	ORR	Recruiting
NCT03825510	II	Metastatic non-small cell lung cancer	3–5 fractions of SBRT	Nivolumab or Pembrolizumab	PD-1 inhibitors start after SBRT	≤3 sites	Single group	OS and acute toxicity	Recruiting
NCT02608385	I	Advanced solid tumors	3 or 5 doses of SBRT	Pembrolizumab	Pembrolizumab is given after SBRT	All sites in Oligometastatic tumors	Arm A: Dose Escalation Cohort. Patients will be enrolled to receive specific doses of SBRT to determine the best safe doses. Arm B: Large Volume Tumors Cohort. Tumors will be partially treated with SBRT. Arm C: Oligometastatic Cohort. All lesions will be treated with SBRT	Recommended SBRT dose in combination with pembrolizumab	Active, not recruiting

We searched “radiation and PD-1/PD-L1 inhibitors” in the clinicaltrials.gov database to identify studies with the following statuses: not yet recruiting, enrolling by invitation, recruiting, active, not recruiting, completed, and unknown status, with study type of interventional (Clinical Trial). A total of >60 trials were identified as trials using radiotherapy with PD-1/PD-L1 inhibitors in advanced metastatic cancers (date of final query, 25 November 2020). Then we searched “radiation and immunotherapy” in the clinicaltrials.gov database as above. A total of >150 trials were detected. We identified the studies of radiotherapy with PD-1/PD-L1 inhibitors in advanced metastatic cancers (date of final query, 25 November 2020). This list shows the trials that allowed more than one lesion irradiated. This list should not be considered comprehensive or exhaustive.

SABR, stereotactic ablative radiotherapy; PFS, progression free survival; CBI, checkpoint blockade immunotherapy; ORR, objective response rate; SBRT, stereotactic body radiotherapy; RCC, renal cell carcinoma; AE, adverse events; DLT, dose limiting toxicities; RT, raidotherapy; TKI, tyrosine kinase inhibitor; NSCLC, non-small-cell lung cancer; SCC, squamous cell carcinoma; HNSCC, head and neck squamous cell carcinoma; ICI, immune checkpoint inhibitor; HCC, hepatocellular carcinoma; OS, overall survival; ACC, adenoid cystic carcinoma; MSS, microsatellite stability.