Table 4 Clinical trials result based on combination therapy with ICIs and other modalities

ICI plus Anti-anti-angiogenic agent

 Triple-negative breast cancer

SHR-1210 plus Apatinib

Notable tolerability and efficacy

Higher TGF-β expressions associated with favorable prognosis

[278]

 Renal cell carcinoma

Atezolizumab plus Bevacizumab

Enhancement in intratumoral CTL cells, and also intra-tumoral MHC-I, Th1, and T-effector markers, and CX3CL1

[279]

 Melanoma

Ipilimumab plus Bevacizumab

Remarkable safety and tolerability

Modification in tumor vasculature and immune responses and alteration of lymphocyte trafficking, and immune regulation

[280]

 Ovarian cancer

Nivolumab plus Bevacizumab

Anti-tumor activity, in particular, in the platinum-sensitive setting

[173]

 Renal cell carcinoma

Nivolumab plus Sunitinib

Remarkable irAEs along with no improvement in the OS

[281]

 Colorectal cancer

Atezolizumab plus Bevacizumab

Without unexpected adverse events or severe toxicities

[282]

 Renal cell carcinoma

Pembrolizumab plus Axitinib

Notable tolerability and efficacy along with no unexpected toxicities

[33]

 Melanoma

Ipilimumab plus Bevacizumab

Improved OS

[283]

 Sarcoma

Nivolumab plus Sunitinib

Improved PFS

[284]

 Non-small cell lung carcinoma

Sintilimab plus Anlotinib

Robust efficacy, durability, and safety profile

Improved PFS

[285]

 Advanced solid tumors

Pembrolizumab plus Lenvatinib

Manageable safety profile and favorable antitumor activity

[286]

 Renal cell carcinoma

Nivolumab plus Cabozantinib

Improved PFS and OS

[287]

 Lymphoma

Solid tumors

Ipilimumab and Lenalidomide

Significant tolerability concomitantly preliminary signals of anti-tumor activity

[288]

 Non-small cell lung carcinoma

Nivolumab plus Bevacizumab

Improved PFS and ORR

[289]

ICI plus Chemotherapeutic agent

 Non-small cell lung carcinoma

Nivolumab plus Ipilimumab and Platinum-based compound

Improved OS versus chemotherapy alone and also favorable risk–benefit profile

[290]

 Solid tumors

Cemiplimab plus RT and CTX

Acceptable safety but no efficacy

[268]

 Non-small cell lung carcinoma

Pembrolizumab plus Carboplatin and Pemetrexed

Improved OS and PFS

[291]

 Non-small cell lung carcinoma

Nivolumab plus Platinum-based compound

Improved OS

[291]

 Non-small cell lung carcinoma

Ipilimumab plus Paclitaxel and Carboplatin

Improved OS and PFS with manageable irAEs

[292]

 Mesothelioma

Nivolumab plus Cisplatin and Pemetrexed

Some irAEs such as severe abdominal distention

[293]

 Pancreatic cancer

Ipilimumab plus Gemcitabine

No superiority over chemotherapy with gemcitabine

[294]

 Biliary tract cancer

Nivolumab plus Gemcitabine and Cisplatin

Improved OS and PFS with manageable irAEs

FasL, MCP-1, and INF-γ associated with favorable prognosis

[149]

 Pancreatic ductal adenocarcinoma

Nivolumab (Nivo) plus nab-Paclitaxel and Gemcitabine

Improved OS along with severe irAEs such as pneumonitis in some case

[295]

 Urothelial cancer

Pembrolizumab plus Docetaxel or Gemcitabine

Improved PFS and ORR

[296]

 Melanoma

Ipilimumab plus Dacarbazine

No tolerability along with high-grade liver toxicities

[297]

ICI plus Radiotherapy

 Melanoma

Ipilimumab plus RT

Synergetic anti-tumor response

[298]

 Melanoma

Ipilimumab plus RT

A systemic complete response

[299]

 Prostate cancer

Ipilimumab plus RT

Complete response in 1 participant only

[300]

 Advanced solid tumors

Nivolumab plus Ipilimumab and RT

Acceptable tolerability along with manageable irAEs

[212]

 Advanced solid tumors

Durvalumab plus RT

Acceptable tolerability without abscopal effect

[301]

 Renal cell carcinoma

Melanoma

Nivolumab plus Ipilimumab and RT

Significant improvement in ORR and OS

Any grade irAEs in 46 of 59 patients

[211]

 Non-small cell lung carcinoma

Pembrolizumab plus RT

Improvement in ORR and OS with an acceptable safety profile

[91]

ICI plus Cancer vaccines

 Melanoma

Ipilimumab plus T-VEC

Improved ORR

[302]

 Melanoma

Ipilimumab plus T-VEC

Improved ORR

[303]

 Prostate cancer

Ipilimumab plus Sipuleucel-T

Acceptable tolerability

[304]

 Prostate cancer

Ipilimumab plus Sipuleucel-T

Improved OS

[304]

 Prostate cancer

Ipilimumab plus GVAX

Improved OS

[305]

 Prostate cancer

Ipilimumab plus GVAX

Manageable irAEs

[306]

 Pancreatic ductal adenocarcinoma

Ipilimumab plus GVAX

Prolonged disease stabilization and a trend of favorable median OS

[200]

 Melanoma

Ipilimumab plus Peptide vaccine

Durable ORR

[307]

 Melanoma

Ipilimumab plus Peptide vaccine

No difference in median OS

[308]

 Melanoma

Pembrolizumab plus T-VEC and RT

No significant effect

[309]

 Melanoma

Nivolumab or Ipilimumab plus T-VEC

Potentiating the antitumor effect of T-VEC

[310]

 Pancreatic ductal adenocarcinoma

Nivolumab plus GVAX and CTX

Improved ORR without any effect on OS

[311, 312]

 Melanoma

Nivolumab plus Gp100

Acceptable tolerability

[313]

ICI plus Other modalities

 Triple-negative breast cancer

Durvalumab plus Olaparib

Acceptable tolerability along with preliminary activity in recurrent cancers

[314]

 Ovarian cancer

Durvalumab plus Olaparib

Modest clinical activity

[315]

 Melanoma

Pembrolizumab plus Dabrafenib and Trametinib

Enhanced anti-tumor responses

[316]

 Renal cell carcinoma

Nivolumab plus Mavorixafor

Potential antitumor activity and a manageable safety profile

[239]