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Table 4 Clinical-stage development of monotherapies and combinatory therapies with immune checkpoint inhibitors in 2021, according to www.clinicaltrials.gov

From: Blockade of novel immune checkpoints and new therapeutic combinations to boost antitumor immunity

Target Drug name Indication Status
CTLA-4 + PD-1 Ipilimumab + nivolumab NSCLC (NCT03351361) (NCT02864251) (NCT02477826) (NCT02869789) (NCT03391869) (NCT04026412) (NCT02998528) (NCT03215706); gastric cancer; GEJ cancer (NCT02872116) (NCT03604991); HNSCC (NCT03700905); metastatic HNSCC (NCT02741570); melanoma (NCT02905266) (NCT02599402) (NCT03068455) (NCT02388906); SCLC (NCT02538666); RCC (NCT03793166) (NCT03873402) (NCT03937219) (NCT03138512) (NCT04513522); esophageal cancer (NCT03143153); sarcoma (NCT04741438); glioblastoma (NCT02017717) (NCT04396860); squamous cell lung cancer (NCT02785952); metastatic urothelial cancer (NCT03036098); metastatic prostate cancer (NCT03879122) Phase III
CTLA-4 + PD-1 Ipilimumab + pembrolizumab Metastatic NSCLC (NCT03302234); metastatic melanoma (NCT01866319); solid tumors (NCT03755739) Phase III
CTLA-4 + PD-1 Ipilimumab + REGN2810 NSCLC (NCT03515629) (NCT03409614) Phase III
CTLA-4 + PD-L1 Tremelimumab + durvalumab Advanced solid tumors (NCT03084471); HNSCC (NCT02369874); NSCLC (NCT02453282); SCLC (NCT03703297); metastatic NSCLC (NCT02542293) (NCT02352948) (NCT03164616); metastatic urothelial cancer (NCT03682068); urothelial cancer (NCT02516241); metastatic HNSCC (NCT02551159); HCC (NCT03298451); squamous cell lung cancer (NCT02154490); RCC (NCT03288532); SCLC (NCT03043872) Phase III
PD-1 + LAG-3 Nivolumab + relatlimab Metastatic melanoma (NCT03470922) Phase III
PD-1 + LAG-3 + B7-H3 MGD013 + enoblituzumab Gastric cancer; GEJ cancer (NCT04082364), metastatic HNSCC (NCT04129320) Phase III
PD-1 + TIGIT Tislelizumab + BGB-A1217 NSCLC (NCT04746924) Phase III
PD-1 + TIGIT Zimberelimab + AB154 Metastatic NSCLC (NCT04736173) Phase III
PD-1 + B7-H3 MGA012 + enoblituzumab Metastatic HNSCC (NCT04129320) Phase III
PD-L1 + TIGIT Atezolizumab + tiragolumab NSCLC (NCT04294810) (NCT04513925); SCLC (NCT04256421) (NCT04665856); esophageal squamous cell carcinoma (NCT04540211) (NCT04543617); Phase III
LAG-3 + PD-1 Relatlimab + nivolumab Multiple solid tumors (NCT01968109); CRC (NCT03642067); metastatic soft-tissue sarcoma (NCT04095208); HNSCC (NCT04080804); NSCLC (NCT04205552) (NCT02750514); RCC (NCT02996110); gastric cancer (NCT02935634); metastatic melanoma (NCT04552223) (NCT03743766) (NCT03724968); solid tumors (NCT03607890); HCC (NCT04567615); metastatic basal cell carcinoma (NCT03521830); HNSCC (NCT04326257); metastatic NSCLC (NCT04623775); metastatic CRC (NCT03867799); GEJ adenocarcinoma (NCT03704077) (NCT03662659) (NCT03610711) (NCT04062656); advanced cancers (NCT03459222) (NCT02488759); metastatic ovarian cancer (NCT046111269); melanoma (NCT02519322); multiple myeloma (NCT04150965) Phase II
LAG-3 + PD-1 BI-754111 + BI-754091 Metastatic solid tumors (NCT03697304) Phase II
LAG-3 + PD-1 REGN3767 + cemiplimab Breast cancer (NCT01042379); metastatic solid tumors (NCT04706715) Phase II
LAG-3 + PD-1 LAG525 + spartalizumab TNBC (NCT03499899); advanced malignancies (NCT03365791) (NCT02460224); melanoma (NCT03484923) Phase II
LAG-3 + PD-1 + TIM-3 INCAGN02385 + INCMGA00012 + INCAGN02390 Advanced malignancies (NCT04370704) Phase II
LAG-3 + PD-1 MK-4280 + pembrolizumab Hodgkin lymphoma; non-Hodgkin lymphoma (NCT03598608); advanced NSCLC (NCT03516981) Phase II
TIM-3 MBG453 Myelodysplastic syndromes; chronic myelomonocytic leukemia (NCT04266301) Phase III
TIM-3 MBG453 AML (NCT04150029) (NCT04623216); advanced solid tumors (NCT02608268); myelofibrosis (NCT04097821) Phase II
TIM-3 + PD-1 BMS-986258 + nivolumab Solid tumors (NCT03446040) Phase II
TIM-3 + PD-1 BGB-A425 + tislelizumab Solid tumors (NCT03744468) Phase II
TIM-3 + PD-1 TSR-022 + TSR-042 Liver cancer (NCT03680508); melanoma (NCT04139902) Phase II
TIGIT + PD-L1 Tiragolumab + atezolizumab Cervical cancer (NCT04300647); gastric adenocarcinoma; GEJ adenocarcinoma; esophageal carcinoma (NCT03281369); urothelial carcinoma (NCT03869190); pancreatic adenocarcinoma (NCT03193190); NSCLC (NCT03563716); metastatic NSCLC (NCT04619797); metastatic HNSCC (NCT04665843); SCLC (NCT04308785); HNSCC (NCT03708224); liver cancer (NCT04524871) Phase II
TIGIT + PD-1 AB154 + zimberelimab NSCLC (NCT04262856) Phase II
TIGIT BMS-986207 Multiple myeloma (NCT04150965) Phase II
TIGIT + PD-1 BMS-986207 + nivolumab Solid tumors (NCT02913313) (NCT04570839) Phase II
PVRIG + PD-1 COM701 + nivolumab Advanced solid tumors (NCT03667716) (NCT04570839) Phase I
KIR2DL1 + KIR2DL2 + KIR2DL3 Lirilumab AML (NCT01687387); chronic lymphocytic leukemia (NCT02481297); refractory AML (NCT02399917) Phase II
KIR2DL1 + KIR2DL2 + KIR2DL3 + PD-1 Lirilumab + nivolumab HNSCC (NCT03341936); metastatic malignancies (NCT03347123); multiple myeloma (NCT01592370); refractory tumors (NCT02813135) Phase II
KIR2DL1 + KIR2DL2 + KIR2DL3 + PD-1 + CTLA-4 Lirilumab + nivolumab + ipilimumab Advanced solid tumors (NCT01714739) Phase II
KIR3DL2 IPH4102 Advanced T cell lymphoma (NCT03902184). Phase II
NKG2A Monalizumab Metastatic HNSCC (NCT04590963) Phase III
NKG2A Monalizumab Metastatic HNSCC (NCT02643550) (NCT03088059); breast cancer (NCT04307329); chronic lymphoid leukemia (NCT02557516) Phase II
NKG2A + PD-L1 Monalizumab + durvalumab CRC (NCT04145193); solid tumors (NCT02671435); NSCLC (NCT03822351) (NCT038223519) (NCT03833440) Phase II
CD200 Samalizumab AML (NCT03013998), multiple myeloma (NCT00648739) Phase II
CD47 Magrolimab Myelodysplastic syndrome (NCT04313881); AML (NCT04778397) Phase III
CD47 + PD-L1 Magrolimab + atezolizumab Metastatic urothelial carcinoma (NCT03869190) Phase II
CD47 Magrolimab Solid tumors (NCT02953782); refractory B-cell non-Hodgkin lymphoma (NCT02953509); myeloid malignancies (NCT04778410) Phase II
CD47 RRX-001 SCLC (NCT03699956) Phase III
CD47 RRX-001 Solid tumors (NCT02489903); metastatic CRC (NCT02096354) Phase II
BTLA JS004 Advanced solid tumors (NCT04278859) Phase I
BTLA TAB004 Advanced solid malignancies (NCT04137900) Phase I
VISTA JNJ-61610588 Advanced solid tumors (NCT02671955) Phase I
VISTA + PD-L1 CA170 Advanced solid tumors and lymphomas (NCT02812875) Phase I
B7-H3 Enoblituzumab Metastatic HNSCC (NCT04129320) Phase III
B7-H3 Enoblituzumab Prostate cancer (NCT02923180) Phase II
B7-H3 131I-omburtamab Neuroblastoma; central nervous system metastases; leptomeningeal metastases (NCT03275402) Phase III
B7-H3 177Lu-DTPA-omburtamab Medulloblastoma (NCT04167618); solid tumors (NCT04315246) Phase II
B7-H3 DS-7300a Advanced solid tumors (NCT04145622) Phase II
B7-H3 + PD-1 MGC018 + MGC012 Advanced solid tumors (NCT03729596) Phase II
  1. NSCLC non-small-cell lung cancer, GEJ gastroesophageal junction, HNSCC head and neck squamous cell carcinoma, SCLC small-cell lung cancer, RCC renal cell carcinoma, HCC hepatocellular carcinoma, MIBC muscle invasive bladder cancer, ESCC esophageal squamous cell carcinoma, TNBC triple-negative breast cancer, CRC colorectal cancer, NMIBC non-muscle invasive bladder cancer, AML acute myeloid leukemia