Table 2C.

The clinical trials of the combination of PD-1/PD-L1 blockade with other ICBs in cancer therapy

Targets	PD-1/PD-L1 blockade	Other ICB	Clinicaltrial no.	Phase	Tumor types	Findings	References
PD-1×LAG-3	Nivolumab	Relatlimab	NCT04205552	II	Resectable NSCLC	Major pathological and objective radiographic responses were achieved in 27% and 10% (nivolumab) and in 30% and 27% (nivolumab and relatlimab) of patients, respectively. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab).	204
PD-1×LAG-3	Nivolumab	Relatlimab	NCT03470922	II/III	Untreated advanced melanoma	The median PFS was 10.1 months; PFS at 12 months was 47.7%.	205
PD-1×LAG-3	Spartalizumab	Ieramilimab	NCT02460224	I/II	Advanced malignancies	Anti-tumor activity was observed in the combination arm, with 3 (2%) complete response and 10 (8%) partial response in a mixed population of tumor types. In the combination arm, eight patients (6.6%) experienced stable disease for 6 months or longer versus six patients (4.5%) in the single-agent arm.	206
PD-1×LAG-3	Tebotelimab		NCT03219268	I	Solid tumors and hematologic cancers	There were tumor decreases in 34% (59/172) of response-evaluable patients in the dose-escalation cohorts, with objective response in multiple solid tumor types, including PD-1-refractory disease, and in LAG-3 non-Hodgkin lymphomas, including CAR-T refractory disease.	207

ICB: immune checkpoint blockades; ORR: objective response rate; DCR: disease control rate; PFS: progression-free survival; NSCLC: non-small cell lung cancer; CAR-T: chimeric antigen receptor T-cell immunotherapy.