TABLE 3.
Clinical trials on novel immune checkpoint inhibitors.
| Target | Drug | Clinical trial no. | Phase | Settings | Tumor types | Treatment arms | Status |
|---|---|---|---|---|---|---|---|
| LAG-3 | Eftilagimod alpha (IMP321) | NCT03252938 | 1 | Advanced/metastatic | Solid tumors | Eftilagimod alpha | Active, not recruiting |
| NCT00351949 | 1 | Advanced/metastatic | RCC | Eftilagimod alpha | Completed | ||
| NCT00349934 | 1 | First line | Breast cancer | Eftilagimod alpha | Completed | ||
| NCT02614833 | 2 | Advanced/metastatic | Breast cancer | Eftilagimod alpha | Active, not recruiting | ||
| NCT00324623 | 1 | Advanced/metastatic | Melanoma | Cyclophosphamide, fludarabine followed by melan-A VLP vaccine and eftilagimod alpha | Completed | ||
| NCT00365937 | 1,2 | Adjuvant | Melanoma | Eftilagimod alphaHLA-A2 peptides | Terminated | ||
| NCT01308294 | 1,2 | Stage II-IV | Melanoma | Eftilagimod alpha+tumor antigenic peptides+monatide | Terminated | ||
| NCT00732082 | 1 | Advanced/metastatic | Pancreatic cancer | Eftilagimod alpha+gemcitabine | Terminated | ||
| NCT02676869 | 1 | Stage III-IV | Melanoma | Eftilagimod alpha+pembrolizumab | Completed | ||
| NCT03625323 | 2 | Advanced/metastatic | NSCLC and HNSCC | Eftilagimod alpha+pembrolizumab | Recruiting | ||
| Relatlimab (BMS-986016) | NCT02966548 | 1 | Advanced/metastatic | Solid tumors | Relatlimabnivolumab | Recruiting | |
| NCT01968109 | 1,2 | First, second line | Solid tumors | Relatlimabnivolumab | Recruiting | ||
| NCT03623854 | 2 | Advanced/metastatic | Chordoma | Relatlimab+nivolumab | Recruiting | ||
| NCT03743766 | 2 | Advanced/metastatic | Melanoma | Relatlimab+nivolumab | Recruiting | ||
| NCT03470922 | 2,3 | Advanced/metastatic | Melanoma | Relatlimabnivolumab | Recruiting | ||
| NCT03642067 | 2 | Advanced/metastatic | MSS CRC | Relatlimab+nivolumab | Recruiting | ||
| NCT04658147 | 1 | Resectable | HCC | Relatlimabnivolumab | Not yet recruiting | ||
| NCT02061761 | 1,2 | Advanced/metastatic | Hematologic malignancies | Relatlimab+nivolumab | Active, not recruiting | ||
| NCT04567615 | 2 | Advanced/metastatic | HCC | Relatlimab+nivolumab | Not yet recruiting | ||
| NCT03607890 | 2 | Advanced, prior PD-(L)1 inhibitor | MSI-H solid tumors | Relatlimab+nivolumab | Recruiting | ||
| NCT04326257 | 2 | Advanced, prior PD-(L)1 inhibitor | HNSCC | Relatlimab+nivolumab or ipilimumab | Recruiting | ||
| NCT03493932 | 1 | Recurrent | Glioblastoma | Relatlimab+nivolumab | Recruiting | ||
| NCT02658981 | 1 | Recurrent | Glioblastoma | Relatlimabnivolumab or urelumab (anti-CD137) | Active, not recruiting | ||
| NCT03610711 | 1,2 | Advanced/metastatic | GC, GEJ cancer | Relatlimabnivolumab | Recruiting | ||
| NCT03044613 | 1 | Stage II/III | GC, GEJ cancer | Nivolumab, carboplatin, paclitaxel, radiationrelatlimab | Recruiting | ||
| NCT03662659 | 2 | Advanced/metastatic | GC, GEJ cancer | Relatlimab or nivolumabinvestigator's choice of chemotherapy | Active, not recruiting | ||
| NCT03335540 | 1,2 | Advanced/metastatic | Solid tumors | Relatlimab+nivolumab or cabiralizumab or ipilimumab or IDO1 inhibitor or radiation therapy | Recruiting | ||
| NCT04611126 | 1,2 | Advanced/metastatic | Ovarian cancer | Relatlimab, nivolumab, cyclophosphamide, fludarabine phosphate, tumor infiltrating lymphocytes infusion ipilimumab | Not yet recruiting | ||
| NCT02488759 | 1,2 | Neoadjuvant and metastatic | Virus-associated tumors | Nivolumabrelatlimab or ipilimumab or daratumumab | Active, not recruiting | ||
| NCT02519322 | 2 | Neoadjuvant and adjuvant | Melanoma | Nivolumabrelatlimab or ipilimumab | Recruiting | ||
| NCT03459222 | 2 | Advanced/metastatic | Solid tumors | Relatlimab, nivolumabipilimumab | Recruiting | ||
| NCT02996110 | 2 | Advanced/metastatic | RCC | Nivolumab+ipilimumab or BMS-986205 (IDO1i) or BMS-813160 (CCR2/5 dual antagonist) | Recruiting | ||
| NCT02935634 | 2 | Advanced/metastatic | GC, GEJ cancer | Nivolumabrelatlimab or ipilimumab or rucaparib or BMS-986205; ipilimumab+ucaparib; nivolumab+ipilimumab+rucaparib | Recruiting | ||
| NCT02750514 | 2 | Advanced/metastatic | NSCLC | Nivolumab relatlimab or ipilimumab or BMS-986205 or dasatinib | Active, not recruiting | ||
| NCT02060188 | 2 | Advanced/metastatic | CRC | Nivolumabrelatimab or daratumumab or ipilimumabcobimetinib | Active, not recruiting | ||
| NCT04150965 | 1,2 | Advanced/metastatic | Multiple myeloma | Relatlimabpomalidromide and dexamethasone; BMS-986207 (anti-TIGIT)pomalidromide and dexamethasone; elotuzumab | Recruiting | ||
| LAG525 | NCT02460224 | 1,2 | Advanced/metastatic | Solid tumors | LAG525spartalizumab (PDR001) | Active, not recruiting | |
| NCT03365791 | 2 | Advanced/metastatic | Solid or hematologic malignancy | LAG525+spartalizumab | Completed | ||
| NCT03742349 | 1 | Advanced/metastatic | TNBC | LAG525+spartalizumab+NIR178 or capmatinib or lacnotuzumab (MCS110) or canakinumab | Recruiting | ||
| NCT03499899 | 2 | Advanced/metastatic | TNBC | LAG525spartalizumabcarboplatin; LAG525+carboplatin | Active, not recruiting | ||
| NCT03484923 | 2 | Advanced/metastatic | Melanoma | Spartalizumab+lag525 or ribociclib or canakinumab or capmatinib | Recruiting | ||
| Cemiplimab (REGN3767) | NCT03005782 | 1 | Advanced/metastatic | Solid tumors or lymphomas | REGN3767cemiplimab (REGN2810) | Recruiting | |
| BI 754111 | NCT03433898 | 1 | Advanced/metastatic | Solid tumors | BI 754111BI 754091 (anti-PD-1) | Recruiting | |
| NCT03156114 | 1 | Advanced/metastatic | Solid tumors | BI 754111+BI 754091 | Active, not recruiting | ||
| NCT03780725 | 1 | Advanced/metastatic | NSCLC and HNSCC | BI 754111+BI 754091 | Completed | ||
| NCT03697304 | 2 | Advanced/metastatic | Solid tumors | BI 754111 or BI 836880 (bispecific VEGF and Ang2 Ab)+BI 754091 (anti-PD-1) | Recruiting | ||
| NCT03964233 | 1 | Advanced/metastatic | Solid tumors | BI 754111+BI 754091BI 907828 (MDM2-p53 antagonist) | Recruiting | ||
| Sym022 | NCT03489369 | 1 | Advanced/metastatic | Solid tumors or lymphomas | Completed | ||
| MGD013 | NCT03219268 | 1 | Advanced/metastatic | Solid or hematologic malignancy | MGD013+margetuximab (anti-HER2 monoclonal antibody) | Recruiting | |
| NCT04082364 | 2,3 | Advanced/metastatic | GC, GEJ cancer | margetuximab+INCMGA00012 (anti-PD-1); margetuximab+chemotherapyMGD013 or INCMGA00012; trastuzumab+chemotherapy (XELOX or mFOLFOX-6) | Recruiting | ||
| Mavezelimab (MK-4280) | NCT03598608 | 1,2 | Measurable disease | Hematologic malignancies | MK-4280+pembrolizumab | Recruiting | |
| NCT02720068 | 1 | Advanced/metastatic | Solid tumors | MK4280+pembrolizumabFOLFIRI or mFOLFOX7 or lenvatinib | Recruiting | ||
| NCT03516981 | 2 | First line | NSCLC | MK4280+pembrolizumab or lenvatinib or quavonlimab (MK-1308) | Recruiting | ||
| TSR-033 | NCT03250832 | 1 | Advanced/metastatic | Solid tumors | TSR-033dostarlimab (TSR-042)mFOLFOX or FOLFIRI | Recruiting | |
| IN-CAGN02385 | NCT03538028 | 1 | Advanced/metastatic | Solid tumors | Completed | ||
| NCT04370704 | 1,2 | Advanced/metastatic | Solid tumors | INCAGN02385+INCAGN02390 (Anti-TIM-3)INCMGA00012 (anti-PD-1) | Recruiting | ||
| NCT03311412 | 1 | Advanced/metastatic | Solid tumors or lymphomas | Sym022+Sym021 (anti-PD-1)Sym023 (anti-TIM-3) | Recruiting | ||
| ECO202 | NCT03600090 | 1 | Advanced/metastatic | Breast cancer | ECO202+paclitaxel | Recruiting | |
| 89Zr-DFO-REGN3767 | NCT04566978 | 1 | Measurable disease by Lugano criteria | DLBCL | Recruiting | ||
| XmAb22,841 | NCT03849469 | 1 | Advanced/metastatic | Solid tumors | XmAb22841pembrolizumab | Recruiting | |
| LBL-007 | NCT04640545 | 1 | Advanced/metastatic | Melanoma | LBL-007+toripalimab (anti-PD-1) | Not yet recruiting | |
| FS118 | NCT03440437 | 1 | Advanced/metastatic | Solid or hematologic malignancy | Active, not recruiting | ||
| RO7247669 | NCT04140500 | 1 | Advanced/metastatic | Solid tumors | Recruiting | ||
| EMB-02 | NCT04618393 | 1,2 | Advanced/metastatic | Solid tumors | Not yet recruiting | ||
| TIGIT | Tiragolumab (MTIG7192A/RG-6058) | NCT02794571 | 1 | Locally advanced or metastatic | Solid tumors | Tiragolumabatezolizumabchemotherapy | Recruiting |
| NCT03563716 | 2 | Locally advanced or metastatic | NSCLC | Atezolizumabtiragolumab | Active, not recruiting | ||
| NCT04294810 | 3 | Locally advanced or metastatic | NSCLC | Atezolizumabtiragolumab | Recruiting | ||
| NCT04256421 | 3 | First line, extensive stage | SCLC | Atezolizumab+carboplatin+etoposidetiragolumab | Recruiting | ||
| NCT03281369 | 1,2 | Advanced/metastatic | Esophageal cancer | Atezolizumab+tiragolumab; atezolizumab+cisplatin/5-FUtiragolumab; cisplatin/5-FU | Recruiting | ||
| GC, GEJ cancer | Atezolizumab+cobimetinib with mFOFLOX6; atezolizumab+cobimetinib or tiragolumab or mFOFLOX or linagliptin or PEGPH20 or BL-8040; pactliaxel+ramucirumab | Recruiting | |||||
| Vibostolimab (MK-7684) | NCT02964013 | 1 | Advanced/metastatic | Solid tumors | Vibostolimabpembrolizumab+pemetrexed/carboplatin; carboplatin+cisplatin+etoposide | Recruiting | |
| NCT04305054 | 1,2 | First line | Melanoma | pembrolizumabvibostolimab or quavonlimab (MK-1308)lenvatinib | Recruiting | ||
| NCT04305041 | 1,2 | Stage III-IV | Melanoma | pembrolizumab+quavonlimab+ vibostolimab or lenvatinib | Recruiting | ||
| NCT04303169 | 1,2 | Stage III | Melanoma | pembrolizumabvibostolimab or V937 (oncolytic virus) | Recruiting | ||
| Etigilimab (OMP-313M32) | NCT03119428 | 1 | Locally advanced or metastatic | Solid tumors | Etigilimabnivolumab | Terminated | |
| BMS-986207 | NCT02913313 | 1,2 | Advanced/metastatic | Solid tumors | BMS-986207nivolumab | Active, not recruiting | |
| NCT04570839 | 1,2 | Advanced/metastatic | Solid tumors | NivolumabBMS-986207 with COM701 (anti-PVRIG Ab) | Recruiting | ||
| Domvanalimab (AB-154) | NCT03628677 | 1 | Advanced/metastatic | Solid tumors | Dombvanalimab+zimberelimab (AB122, anti-PD-1) | Recruiting | |
| NCT04262856 | 2 | Locally advanced or metastatic | NSCLC | Zimberelimabdombvanalimabetrumadenant | Recruiting | ||
| ASP-8374 | NCT03945253 | 1 | Advanced/metastatic | Solid tumors | Completed | ||
| NCT03260322 | 1 | Advanced/metastatic | Solid tumors | ASP-8374pembrolizumab | Active, not recruiting | ||
| IBI939 | NCT04353830 | 1 | Advanced/metastatic | Solid tumors | IBI939sintilimab (anti-PD-1) | Recruiting | |
| NCT04672369 | 1 | Advanced/metastatic | NSCLC | IBI939sintilimab | Not yet recruiting | ||
| NCT04672356 | 1 | Advanced/metastatic | NSCLC and SCLC | IBI939sintilimab | Not yet recruiting | ||
| BGB-A1217 | NCT04047862 | 1 | Advanced/metastatic | Solid tumors | BGB-A1217+tiselizumabchemotherapy | Recruiting | |
| COM902 | NCT04354246 | 1 | Advanced/metastatic | Solid tumors | Recruiting | ||
| M6223 | NCT04457778 | 1 | Advanced/metastatic | Solid tumors | M6223bintrafusp alfa (M7824) | Recruiting | |
| TIM-3 | Sym023 | NCT03489343 | 1 | Advanced/metastatic | Solid tumors or lymphomas | Completed | |
| LY3321367 | NCT03099109 | 1 | Advanced/metastatic | Solid tumors | LY3300054 (anti-PD-L1)+LY3321367 | Active, not recruiting | |
| NCT02791334 | 1 | Advanced/metastatic | Solid tumors | LY3300054LY3321367 or abemaciclib or ramucirumab or merestinib | Active, not recruiting | ||
| Cobolimab (TSR-022) | NCT02817633 | 1 | Advanced/metastatic | Solid tumors | Cobolimabnivolumab or TSR-042TSR-033docetaxel | Recruiting | |
| NCT03307785 | 1 | Advanced/metastatic | Solid tumors | Dostarlimab (TSR-042)TSR-022+chemotherapy a ; dostarlimab+bevacizumabniraparib or chemotherapy a | Active, not recruiting | ||
| NCT03680508 | 2 | BCLC stage B or C | HCC | Cobolimab+dostarlimab | Recruiting | ||
| NCT04139902 | 2 | Neoadjuvant | Melanoma | Cobolimabdostarlimab | Recruiting | ||
| Sabatolimab (MBG453) | NCT02608268 | 1,2 | Advanced/metastatic | Solid tumors | Sabatolimabspartalizumab; decitabine | Active, not recruiting | |
| NCT03961971 | 1 | Advanced/metastatic | GBM | Sabatolimab+spartalizumab | Recruiting | ||
| NCT04623216 | 1,2 | Received one prior aHSCT | AML | Sabatolimabazacitidine | Not yet recruiting | ||
| NCT03066648 | 1 | Relapse/refractory | AML or high risk MDS | Sabatolimabspartalizumabdecitabine | Recruiting | ||
| NCT03940352 | 1 | Relapse/refractory | AML or high risk MDS | HDM201 (p53-MDM2 inhibitor)+sabatolimab or venetoclax | Recruiting | ||
| NCT03946670 | 2 | IPSS-R intermediate, high, or very high risk | MDS | hypomethylating agentssabatolimab | Active, not recruiting | ||
| NCT04266301 | 3 | IPSS-R intermediate, high, or very high risk for MDS | MDS or CML | Sabatolimab+azacitidine | Recruiting | ||
| INCAGN2390 | NCT03652077 | 1 | Advanced/metastatic | Solid tumors | Active, not recruiting | ||
| BMS-986258 | NCT03446040 | 1,2 | Advanced/metastatic | Solid tumors | BMS-986258+nivolumab or rHuPH20 | Recruiting | |
| SHR-1702 | NCT03871855 | 1 | Advanced/metastatic | Solid tumors | SHR-1702camrelizumab | Unknown | |
| RO7121661 | NCT03708328 | 1 | Advanced/metastatic | Solid tumors | Recruiting | ||
| B7-H3 | Enoblituzumab (MGA271) | NCT01391143 | 1 | Advanced/metastatic | Solid tumors | Completed | |
| NCT02982941 | 1 | Advanced/metastatic | Pediatric solid tumors | Completed | |||
| NCT02923180 | 2 | Localized intermediate and high-risk | Prostate cancer | Active, not recruiting | |||
| NCT04634825 | 2 | Advanced/metastatic | HNSCC | Enoblituzumab+retifanlimab (anti-PD-1 antibody) or tebotelimab (PD-1 and LAG-3 bispecific DART molecule) | Not yet recruiting | ||
| NCT02381314 | 1 | Advanced/metastatic | Solid tumors | Enoblituzumab+ipilimumab | Completed | ||
| NCT02475213 | 1 | Advanced/metastatic | Solid tumors | Enoblituzumab+pembrolizumab or retifanlimab | Active, not recruiting | ||
| NCT04129320 | 2,3 | Advanced/metastatic | HNSCC | Enoblituzumab+retifanlimab or tebotelimab | Withdrawn | ||
| DS-7300a | NCT04145622 | 1,2 | Advanced/metastatic | Solid tumors | Recruiting | ||
| Orlotamab (MGD009) | NCT02628535 | 1 | Advanced/metastatic | solid tumors | Terminated | ||
| NCT03406949 | 1 | Advanced/metastatic | Solid tumors | Orlotamab+retifanlimab | Active, not recruiting | ||
| 131I-Omburtamab | NCT01099644 | 1 | Peritoneal involvement | DSRCT | Active, not recruiting | ||
| NCT00089245 | 1 | Advanced/metastatic | CNS or leptomeningeal cancer | Active, not recruiting | |||
| NCT03275402 | 2,3 | Recurrent | Neuroblastoma, CNS, or leptomeningeal metastases | Recruiting | |||
| 124I-Omburtamab | NCT01502917 | 1 | Prior external beam radiotherapy | Gliomas | 124I-Omburtamab+external beam radiotherapy (prior to study entry) | Recruiting | |
| 177Lu-DTPA-Omburtamab | NCT04167618 | 1,2 | Recurrent | Medulloblastoma | Not yet recruiting | ||
| NCT04315246 | 1,2 | Advanced/metastatic | Leptomeningeal metastasis from solid tumors | Not yet recruiting | |||
| 4SCAR-276 | NCT04432649 | 1 | Advanced/metastatic | Solid tumors | Recruiting | ||
| SCRI-CARB7H3 | NCT04185038 | 1 | Advanced/metastatic | Pediatric CNS tumors | Recruiting | ||
| B7-H3 CAR-T | NCT04385173 | 1 | Recurrent | GBM | B7-H3 CAR-T+temozolomide | Recruiting | |
| NCT04077866 | 1,2 | Recurrent | GBM | B7-H3 CAR-Ttemozolomide | Recruiting | ||
| CAR.B7-H3 | NCT04670068 | 1 | Advanced/metastatic | Epithelial ovarian cancer | B7-H3 CAR-T+fludarabine+cyclophosphamide | Not yet recruiting | |
| Second generation 4-1BB B7H3-EGFRt-DHFR | NCT04483778 | 1 | Recurrent | Non-primary CNS solid tumors | Second generation 4-1BB B7H3-EGFRt-DHFRsecond generation 4-1BB CD19-Her2tG | Recruiting | |
| VISTA | JNJ-61610588 | NCT02671955 | 1 | Advanced/metastatic | Solid tumors | Terminated | |
| CI-8993 | NCT04475523 | 1 | Advanced/metastatic | Solid tumors | Recruiting | ||
| CA-170 | NCT02812875 | 1 | Advanced/metastatic | Solid tumors or lymphomas | Completed | ||
| ICOS | GSK3359609 | NCT04428333 | 1,2 | Advanced/metastatic | HNSCC | GSK3359609pembrolizumab+fluouracil-platinum based chemotherapy | Recruiting |
| NCT04128696 | 3 | Advanced/metastatic | HNSCC | GSK3359609+pembrolizumab | Recruiting | ||
| NCT03693612 | 2 | Advanced/metastatic | Solid tumors | GSK3359609+pembrolizumab; docetaxel+paclitaxel+cetuximab | Recruiting | ||
| JTX-2011 | NCT02904226 | 1,2 | Advanced/metastatic | Solid tumors | JTX-2011+pembrolizumab or nivolumab or ipilimumab | Completed | |
| MEDI-570 | NCT02520791 | 1 | Advanced/metastatic | Lymphoma | Recruiting | ||
| KY1044 | NCT03829501 | 1,2 | Advanced/metastatic | Solid tumors | KY1044atezolizumab | Recruiting | |
| BTLA | INBRX-106 | NCT04198766 | 1 | Locally advanced or metastatic | Solid tumors | INBRX-106+pembrolizumab | Recruiting |
| Cudarolimab (IBI101) | NCT03758001 | 1 | Advanced/metastatic | Solid tumors | Cudarolimab+sintilimab (anti-PD-1) | Recruiting | |
| PF-04518600 | NCT02315066 | 1 | Advanced/metastatic | Solid tumors | PF-04518600utomilumab (PF-05082566, anti-TNFRSF9) | Completed | |
| TAB004 (JS004) | NCT04137900 | 1 | Advanced/metastatic | Solid tumors or lymphomas | Recruiting | ||
| NCT04278859 | 1 | Advanced/metastatic | Solid tumors | Recruiting | |||
| NCT04477772 | 1 | Advanced/metastatic | Lymphoma | Recruiting |
Abbreviations: AML, acute myeloid leukemia; anti-PD-1, anti-programmed death-1; BCLC, Barcelona Clinic Liver Stage; BTLA, B and T-lymphocyte attenuator; CML, chronic myelogenous leukemia; CNS, central nervous system; CRC, colorectal cancer; DART, dual-affinity re-targeting proteins; DLBCL, diffuse large B cell lymphoma; DSRCT, desmoplastic small round cell tumor; GBM, glioblastoma multiforme; GC, gastric cancer; GEJ, gastroesophageal junction cancer; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous cell carcinoma; ICOS, Inducible T cell costimulator; IDO1i, indoleamine 2,3-dioxygenase-1 inhibitor; IPSS-R, revised international prognostic scoring system; LAG3, lymphocyte-associated gene 3; MDM2, mouse double minute 2 homolog; MDS, myelodysplastic syndrome; MSI-H, microsatellite instability-high; MSS, microsatellite stable; NSCLC, non-small cell lung cancer; PEGPH20, pegylated recombinant human hyaluronidase; RCC, Renal cell carcinoma; rHuPH20, recombinant human hyaluronidase PH20 enzyme; SCLC, small cell lung carcinoma; TIGIT, T cell immunoglobulin and ITIM domain; TIM, T-cell immunoglobulin and mucin domain-3; TNBC, triple negative breast cancer; TNFRSF9, tumor necrosis factor receptor superfamily member 9; VEGF, vascular endothelial growth factor; VISTA, V-domain immunoglobulin suppressor of T cell activation.
Regimens: mFOLFOX, oxaliplatin 85mg/m2 intravenous (IV), leucovorin 400mg/m2 IV, and fluorouracil 2400mg/m2 IV over 4648h every 2weeks (Q2W) FOLFIRI, irinotecan 180mg/m2 IV, leucovorin 400mg/m2 IV, and 5-FU 2400mg/m2 IV over 4648h (Q2W).
a
Chemotherapy: carboplatin/pemetrexed, carboplatin/nab-paclitaxel, or carboplatin/paclitaxel.