Introduction
Structural characteristics and biological functions of LAG-3, TIM-3, and TIGIT
IC | Ligands | Expression | Mechanism of action | Ref. |
---|---|---|---|---|
LAG-3 | MHC-II | B cells, MON-Mø, DCs, some activated T cells | Negatively regulates T cell responses | [24] |
FGL-1 | FGL-1 protein is primarily secreted from hepatocytes | Inhibiting antitumor immune responses | [28] | |
α-synuclein | Neurons, heart, muscle, and other tissues | LAG-3 can recognize α-synuclein fibrils and affect its endocytosis and intercellular transmission, contributing to PD | [223] | |
Gal-3 | Tumor cells, macrophages, epithelial cells, fibroblasts, activated T cells | Inhibiting antitumor T cell responses | [27] | |
Tim-3 | LSECtin | Liver, tumor-associated macrophages, and other tumor tissues | Inhibiting antitumor T cell responses | [26] |
Gal-9 | APC, MDSCs, Naive CD4 T cells, plasma | Gal-9 mainly induces calcium to flow into the intracellular area of Th1 cells and induces apoptosis | [224] | |
PtdSer | Released from apoptotic cells | PtdSer and TIM-3 binding contributes to the clearance of apoptotic bodies and antigen cross-presentation by Tim-3+ DCs | [104] | |
CEACAM-1 | DCs, monocytes, macrophages, and activated T cells | CEACAM-1/TIM-3 complex formation has a crucial role in regulating autoimmunity and antitumor immunity | [102] | |
HMGB1 | Proliferating tissues or estrogen stimulated cancer cells | Blocking activation and suppresses innate immune responses to nucleic acids | [103] | |
TIGIT | CD155 | DCs, T cells, B cells, macrophages | Increasing the IL-10 secretion | [51] |
CD113 | Liver, testes, lungs, placenta, and kidneys | Inhibition of T cell and NK cell activity | [121] | |
CD112 | Hematopoietic and non-hematopoietic tissues | Inhibiting the activation of T cells and NK cells | [225] | |
Nectin4 | Tumor cells | Inhibiting NK cell activity | [55] | |
Fap2 | Tumor cells | Inhibiting NK cell toxicity and T cell activity | [56] |
LAG-3
TIM-3
TIGIT
Upregulating the expression of LAG-3, TIM-3 and TIGIT in solid tumors and leukemia
IC | Expression on immune cells | Expression on tumor cells | disease | Association with Clinical outcome | Ref. |
---|---|---|---|---|---|
LAG-3 | Activated CD4+ and CD8+ T cells | – | Melanoma | Impairs immune cells function and antitumor immune response | |
TILs | – | NSCLC | Associate with a worse prognosis | [3] | |
TILs | – | HNSCC | High pathological grade, larger tumor size and positive lymph node status | ||
Peripheral CD4+ and CD8+ T cells, TILs | – | STS | High pathological grades, advanced tumor stage, and poor prognosis | [7] | |
CD8+ TIL, DC | – | RCC | Associated with a poorer prognosis for RCC in humans | [78] | |
TILs, tumor-associated perivascular lymphocytes | – | Glioblastoma | Correlated with significantly less IFN-γ release upon activation and is a marker of T cell exhaustion | ||
TILs | – | HCC | Positively associated with more types of cirrhosis and advanced cancer | ||
TILs | – | PAAD | Significantly reduce disease-free survival in patients | ||
Leukemia-tolerant CD8+ T cells | Leukemia cells | HMs | Promoting T cell dysfunction | [4] | |
CD4+/CD8+ T cells | – | GC | Improve the prognosis of patients with advanced gastric cancer who receive anti-programmed death-1 antibody therapy | [67] | |
TILs at the tumor front | – | Stage II CRCA | Predict better treatment outcomes in both the entire stage II and the subgroup of stage II microsatellite-stable tumors | [84] | |
TILs | – | TNBC, Her2 + BC | The infiltration of LAG-3 lymphocytes ameliorates OS in TNBC and Her2 + BC | [7] | |
CD4+ Tregs, CD8+ T cells, TAMss | Malignant B cell | DLBCL | Associated with poor survival and poor prognosis | [25] | |
TIM-3 | Mast cells, antigen-specific CD8+ T cells, NK cells | Melanoma cells | Melanomas | Promote tumor progression | |
TADCs, TILs | Tumor cells | Lung cancer | Lower survival | ||
TADCs, CD8+TILs | MC38 cells, colon cancer cells, tumor tissues | CC | Poor prognosis and Inhibition of tumor progression | ||
TILs, TAMs, APC | HCC, HBV-associated HCC | HCC | Lower survival, paralleled the grades of HCC, Immunotherapy resistance | ||
CD8+ TILs | Lymphoma endothelial cells | NHL | Promote tumor progression | ||
CD4+, CD8+T cells | LSCs | AML, MDS | Poor prognosis and relapse after allo-HSCT | ||
TIGIT | CD8+T cells | – | AML | TIGIT expression on CD8+ T cells is elevated in AML patients and high-TIGIT correlates with primary refractory disease and leukemia relapse post-allo-SCT | [111] |
CD8+T cells | – | GC | Promote the development of advanced GC | [112] | |
CD8+T cells | – | MM | Reduced tumor burden and improved survival | [230] | |
CD8+TILs | CC | CRCA | Promote tumor growth | [54] | |
CTLs | MCL | MCL | This led to a relapse after CAR-T cell therapy | [215] | |
CD8+T cells | – | ESCC | Coexpression of TIGIT and PD-L1 leads to poor OS | [231] |
LAG-3
TIM-3
TIGIT
Preclinical studies evaluating therapies targeting LAG-3, TIM-3, and TIGIT in solid tumors and leukemia
LAG-3
TIM-3
TIGIT
Clinical trials of anti-LAG-3, anti-TIM-3, and anti-TIGIT mAbs
Anti-LAG-3 mAbs
Clinical trial identifier | Phase | Start date | Status | Cancer type (population, N) | Interventions and Combination | Target | Primary Outcome Measures | Secondary Outcome Measures |
---|---|---|---|---|---|---|---|---|
NCT0206176 | I/II | Mar 13, 2014 | Completed | HMs, N = 106 | Relatlimab | LAG-3 | AEs, SAEs | Cmax, Tmax |
NCT02720068 | I | May 2, 2016 | Active, not recruiting | Neoplasms, N = 576 | Favezelimab | LAG-3 | DLTs, AEs | ORR |
NCT03005782 | I | Nov 7, 2016 | Active, not recruiting | Malignancies, N = 333 | REGN3767 | LAG-3 | Cmax, Tmax | RECIST |
NCT04566978 | I | Sep 11, 2020 | Recruiting | DLBCL, N = 20 | 89Zr-DFO-REGN3767 | LAG-3 | Biodistribution | – |
NCT03489369 | I | May 8, 2018 | Completed | Metastatic Cancer Solid Tumor Lymphoma, N = 15 | Sym022 | LAG-3 | AEs | OR, SD, TTP |
NCT02195349 | I | Jul 30, 2014 | Completed | Psoriasis, N = 67 | GSK2831781 | LAG-3 | PCI, AEs, SAEs | PASI, PGA |
NCT02460224 | I/II | Jun 17, 2015 | Completed | Advanced Solid Tumor, N = 490 | LAG525 | LAG-3 | DLTs, ORR | AEs, RDI |
NCT03250832 | I | Aug 8, 2017 | Completed | Neoplasms, N = 111 | TSR-033 | LAG-3 | SAEs, TEAEs | AUC, Cmax |
NCT03538028 | I | Jun 18, 2018 | Completed | MSI-High Endometrial Cancer, CCA, GC, N = 22 | INCAGN02385 | LAG-3 | TEAEs | Cmax, Tmax, ORR |
NCT02935634 | II | Nov 29, 2016 | Completed | AGC, N = 190 | Relatlimab + Nivolumab | LAG-3 PD-1 | ORR, DOR | AEs |
NCT02488759 | I/II | Oct 13, 2015 | Completed | Various Advanced Cancers, N = 578 | AEs, ORR | DOR, OS | ||
NCT02996110 | II | Feb 2, 2017 | Completed | Advanced Cancer, N = 182 | ORR, DOR | AEs | ||
NCT02519322 | II | Feb 2, 2016 | Completed | CM, MM, OM, N = 53 | OS | |||
NCT02061761 | I/II | Mar 13, 2014 | Completed | HMs, N = 106 | AEs | Cmax, Tmax | ||
NCT03310619 | I/II | Nov 28, 2017 | Completed | NHL, DLBCL, FL, N = 62 | JCAR017 + Relatlimab | LAG-3 CD19 | DLTs | AEs, PFS |
NCT04112498 | I | Oct 1, 2019 | Completed | Cancer, N = 24 | Relatlimab + rHuPH20 + Nivolumab | LAG-3 CD38 PD-1 | Cmax, SAEs | AEs |
NCT04626518 | II | Dec 17, 2020 | Recruiting | ccRCC, N = 370 | Favezelimab + Pembrolizumab | LAG-3 PD-1 | DLTs, AEs | DOR, PFS |
NCT05342636 | I/II | Jul 27, 2022 | Recruiting | ESCC, N = 120 | DLTs, AEs | PFS, DOR | ||
NCT04938817 | I/II | Aug 19, 2021 | Active, not recruiting | SCLC, N = 80 | AEs, ORR | PFS, DOR | ||
NCT02625961 | II | Feb 10, 2016 | Recruiting | BC, N = 320 | DFS | DOR | ||
NCT05845814 | I/II | Jul 10, 2023 | Recruiting | mUC, UN, N = 390 | ORR, AEs | PFS, DOR | ||
NCT03516981 | II | Oct 1, 2018 | Active, not recruiting | Advanced NSCLC, N = 318 | ORR | PFS, OS | ||
NCT02720068 | I | May 2, 2016 | Active, not recruiting | Neoplasms, N = 576 | DLTs, AEs | ORR | ||
NCT03598608 | I/II | Oct 17, 2018 | Recruiting | NHL, DLBCL, N = 174 | DLTs, AEs | ORR | ||
NCT05508867 | III | Oct 18, 2022 | Recruiting | NHL, N = 360 | PFS | OS, ORR | ||
NCT05064059 | III | Nov 10, 2021 | Active, not recruiting | CRC, N = 432 | OS | PFS, ORR | ||
NCT05600309 | III | Jun 14, 2022 | Recruiting | CRC, N = 94 | OS | PFS, ORR | ||
NCT05137054 | I | Aug 17, 2022 | Recruiting | MM, N = 317 | REGN3767 + Linvoseltamab | LAG-3 BCMA CD3 | DLTs, TEAEs | ORR, DOR |
NCT01042379 | II | Mar 1, 2010 | Recruiting | BC, N = 5000 | REGN3767 + Cemiplimab | LAG-3 PD-1 | pCR | RCB, RFS |
NCT03916627 | II | Jul 23, 2019 | Recruiting | NSCLC, HCC, HNSCC Carcinoma, N = 73CLC | MPR, STN | ORR, OS | ||
NCT05785767 | II/III | Jun 16, 2023 | Recruiting | Advanced NSCLC, N = 850 | ORR, OS | TEAEs, SAEs | ||
NCT05352672 | III | Jul 14, 2022 | Recruiting | Melanoma, N = 1590 | PFS | OS, DCR | ||
NCT03005782 | I | Nov 7, 2016 | Active, not recruiting | Malignancies, N = 333 | AUC, CL | ORR | ||
NCT03311412 | I | Nov 20, 2017 | Completed | Metastatic Cancer, Solid Tumor, Lymphoma, N = 89 | Sym022 + Sym021 + Sym023 | LAG-3 PD-1 Tim-3 | AEs | OR, SD |
NCT04641871 | I | Oct 12, 2020 | Active, not recruiting | Metastatic Cancer, Solid Tumor, N = 148 | Sym022 + Sym021 | LAG-3 PD-1 | ORR, SAEs | Cmax, AUC |
NCT03484923 | II | Sep 10, 2018 | Completed | Melanoma, N = 196 | LAG525 + Spartalizumab | LAG-3 PD-1 | ORR | OS, PFS |
NCT03499899 | II | Jul 2, 2018 | Completed | TNBC, N = 88 | LAG525 + PDR001 + Carboplatin | LAG-3 PD-1 | ORR | CBR, DOR |
NCT02460224 | I/II | Jun 17, 2015 | Completed | Advanced Solid Tumors, N = 490 | LAG525 + PDR001 | LAG-3 PD-1 | DLTs, ORR | AEs, Cmax |
NCT03365791 | II | Jan 24, 2018 | Completed | SCLC, GAC, EAC, CRPC Adenocarcinoma, N = 76 | CBR | ORR, TTR | ||
NCT03250832 | I | Aug 8, 2017 | Completed | Neoplasms, N = 111 | TSR-033 + Dostarlimab + mFOLFOX6 + FOLFIRI + Bevacizumab | LAG-3 PD-1 VEGF-A | SAEs, TEAEs | AUC, Cmax |
NCT04463771 | II | Jan 26, 2021 | Recruiting | UCEC, N = 300 | INCAGN02385 + INCMGA00012 | LAG-3 PD-1 | ORR | CR, OS |
NCT04370704 | I/II | Jul 27, 2020 | Recruiting | Melanoma, N = 146 | INCAGN02385 + INCAGN02390 + INCMGA00012 | LAG-3 PD-1 Tim-3 | TEAEs, ORR | DCR |
NCT05287113 | II | Nov 14, 2022 | Recruiting | HNSC, N = 162 | INCAGN02385 + Retifanlimab | LAG-3 PD-1 | PFS | ORR, DOR, etc |
Anti-TIM-3 mAbs
Clinical trial identifier | Phase | Start date | Status | Cancer type (population, N) | Interventions and Combination | Target | Primary Outcome Measures | Secondary Outcome Measures |
---|---|---|---|---|---|---|---|---|
NCT05738980 | Not Applicable | Feb 1, 2023 | Recruiting | HCC, N = 88 | Auto-anti-TIM-3-blocked RAK cells | TIM-3 | RFS | OS |
NCT03489343 | I | May 24, 2018 | Completed | Advanced Solid Tumor or Lymphomas, N = 24 | Sym023 | TIM-3 | AEs, DLTs | Immunogenicity, OR, SD, TTP |
NCT04623892 | I | Dec 01, 2020 | Unknown | Advanced Solid Tumors, N = 50 | TQB2618 | TIM-3 | MTD | Tmax, Cmax, ORR, PFS, DOR, DCR |
NCT04823624 | II | Sep 2021 | Unknown | Lower Risk MDS, N = 20 | MBG453 | TIM-3 | ORR, | TEAEs, PFS, OS |
NCT03652077 | I | Sep 24, 2018 | Completed | Select Advanced Malignancies, N = 40 | INCAGN02390 | TIM-3 | AEs, Tmax, PAD | Immunogenicity, ORR, DOR, DCR, PFS, Cmax, Tmax |
NCT05020912 | II | Dec 13, 2021 | Completed | HR/vHR MDS, N = 20 | MBG453 + azacytidine + venetoclax | TIM-3 | DLTs, CRR | CR, ORR, PFS, OS |
NCT03946670 | II | Jun 4, 2019 | Active, not recruiting | IM/H/VH-MDS, N = 127 | MBG453 + HMAs | TIM-3 | CRR, PFS | OS, LFS, ORR, DCR |
NCT04623216 | I/II | Sep 14, 2021 | Recruiting | AML/AML MRD + post-aHSCT, N = 59 | MBG453 + Azacitidine | TIM-3 | DLTs, CRR | grade III or IV aGvHD, cGvHD, ADA, Cmax, iR-AEs |
NCT04878432 | II | Mar 17, 2022 | Recruiting | IM/H/VH-MDS, N = 90 | MBG453 + HMA | TIM-3 | TEAEs, SAEs | CRR, OS, PFS, LFS, DOR |
NCT04266301 | III | Jun 8, 2020 | Active, not | IM/H/VH-MDS, CMML-2, N = 530 | MBG453 + Azacitidine | TIM-3 | OS | Safety, CR, etc. |
NCT04443751 | I | Sep 10, 2020 | Recruiting | R/R-AML, HR-MDS, N = 42 | SHR-1702 | TIM-3 | MTD, RP2D | Safety, PK, etc. |
NCT04150029 | II | Sep 1, 2020 | recruiting | ND-AML, N = 86 | MBG453 + HMA + Venetoclax | TIM-3 | Safety, DLTs CR rate | CR/CRi rate, OS, etc. |
NCT04812548 | II | May 31, 2021 | Not yet recruiting | HR-MDS, N = 76 | MBG453 + HMA + Venetoclax | TIM-3 | Safety, DLTs, CR rate | ORR, PFS, etc. |
CTR20201781 | III | Aug 6, 2020 | recruiting | HR-MDS, CMML-2, N = 100 | MBG453 + Azacitidine | TIM-3 | OS | Safety, CR, etc. |
NCT03680508 | II | Dec 19, 2019 | Recruiting | HCC, N = 42 | TSR-022 + TSR-042 | TIM-3, PD-1 | ORR | irRC, DOR, TTP PFS, OS |
NCT03311412 | I | Nov 20, 2017 | Completed | Advanced Solid Tumor or Lymphomas, N = 89 | Sym023 ± Sym021 | TIM-3, PD-1 | AEs, DLTs | Immunogenicity, OR, SD, TTP |
NCT03099109 | Ia/Ib | Apr 12, 2017 | Active, not recruiting | advanced relapsed/refractory solid tumors, N = 275 | LY3300054 ± LY3321367 | TIM-3, PD-L1 | DLTs | PK, ORR, PFS, DOR, TTP, DCR |
NCT02608268 | I-Ib/II | Nov 23, 2015 | Terminated | Advanced Malignancies, N = 252 | PDR001 ± MBG453 | TIM-3, PD-1 | Safety, ORR, DLTs | BOR, Cmax, DOR, OS, PFS, irRC |
NCT02817633 | I | Jul 8, 2016 | Recruiting | Advanced Solid Tumors, N = 475 | TSR-042 ± TSR-022 | TIM-3, PD-1 | DLTs, AEs, SAEs, TEAEs, irAEs, ORR | ORR, DOR, DCR, PFS, OS |
NCT04641871 | I | Oct 12, 2020 | Active, not recruiting | BTC, ESCC, N = 148 | Sym021 + Sym023 + irinotecan | TIM-3, PD-1 | ORR, AEs, SAEs | Cmax, Tmax, ORR, DOR, DCR, PFS, OS |
NCT05645315 | Ib | Apr 28, 2022 | Recruiting | Advanced Solid Tumors, N = 127 | TQB2618 + TQB2450 | TIM-3, PD-L1 | ORR, DLTs | Immunogenicity, PFS, OS, DCR, AEs |
NCT05563480 | II | Oct 27, 2022 | Recruiting | R/M NPC, N = 90 | TQB2618 + Penpulimab | TIM-3, PD-1 | MTD, ORR, PFS | OS, DCR, DOR, AEs, SAEs |
NCT03066648 | Ib | Jul 6, 2017 | Active, not recruiting | AML/HR-MDS, N = 241 | PDR001 ± MBG453 with HMA | TIM-3, PD-1 | AEs, SAEs, DLTs | ORR, DOR, DCR, PFS, TTP, Cmax, Tmax, Half-life |
NCT05834543 | Ib | May 2023 | Not yet recruiting | Advanced ESCC, N = 75 | TQB2618 + Penpulimab + Chemotherapy | TIM-3, PD-1 | PFS, ORR | OS, DCR, DOR, AEs, SAEs |
NCT05451407 | I | Aug 9, 2022 | Not yet recruiting | Advanced Melanoma, N = 50 | TQB2618 + Toripalimab | TIM-3, PD-1 | DLTs, ORR | PFS, OS, DCR |
NCT04139902 | II | Jun 12, 2020 | Recruiting | operable melanoma, N = 56 | TSR-022 ± TSR-042 | TIM-3, PD-1 | MPR | PFS, OS, AEs, Frequency of Delays in Surgery |
NCT05400876 | Ib | Jun 9, 2022 | Recruiting | R/R Lymphoma, N = 92 | TQB2618 + Penpulimab | TIM-3, PD-1 | DLTs, ORR | CRR, DCR, DOR, PFS, OS, AEs |
NCT03940352 | I | Jun 24, 2019 | Active, not recruiting | AML, HR-MDS, N = 52 | MBG453 + HDM201 | TIM-3, p53-MDM2 | AEs, SAEs, DLTs | ORR, BOR, PFS |
NCT05783921 | I/II | Mar 2023 | Not yet recruiting | R/M-HNSCCs, N = 60 | TQB2618 + Penpulimab + Chemotherapy | TIM-3, PD-1 | PFS, ORR | PFS, OS, DOR, DCR, CBR, AEs, SAEs |
NCT03961971 | I | Feb 18, 2020 | Active, not recruiting | Recurrent GBM, N = 16 | MBG453 + Spartalizumab + Stereotactic radiosurgery SRS | TIM-3, PD-1 | SAEs | grade 3 or higher toxicity, PFS, OS, ORR |
NCT05367401 | I/II | Dec 20, 2024 | Not yet recruiting | Unfit ND-AML/HR-MDS/R/R-AML, N = 63 | MBG453 + Magrolimab + Azacitidine | TIM-3, CD47 | DLTs, CR | ADA, Cmax, Time from first CR to relapse or death, CRR |
NCT04370704 | I/II | Jul 27, 2020 | Recruiting | Melanoma, N = 146 | INCAGN02385 INCAGN02390 + INCMGA00012 | TIM-3, PD-1, LAG-3 | TEAEs, ORR, DOR, DCR, PFS | ORR, DCR, PFS |
NCT04810611 | I | Jun 18, 2021 | Recruiting | LR-MDS, N = 90 | MBG453 ± NIS793 ± Canakinumab | TIM-3, TGF-β, IL-1β | DLTs, AEs, SAEs | BOR, TTP DOR, PFS, ORR |
NCT03744468 | I/II | Nov 13, 2018 | Recruiting | Advanced Solid Tumors, N = 358 | BGB-A425 + Tislelizumab + LBL-007 | TIM-3, PD-1, LAG-3 | TEAEs, SAEs, MTD, ORR | DOR, DCR, PFS, PK, Cmax |
NCT04586244 | II | Jan 14, 2022 | Recruiting | Urothelial Carcinoma, N = 45 | INCAGN02390 + INCAGN02385 + Retifanlimab | TIM-3, LAG-3, PD-1 | CD8 + lymphocytes changes | TEAEs, pCR, MPR |
NCT05287113 | II | Nov 14, 2022 | Recruiting | PD-L1-Positive R/M-HNSCCs, N = 162 | Retifanlimab + INCAGN02385 + INCAGN02390 | TIM-3, LAG-3, PD-1 | PFS | ORR, DOR, DCR, OS, TEAEs |
NCT03307785 | I | Oct 12, 2017 | Active, not recruiting | Advanced or Metastatic Cancer, N = 58 | TSR-022 + TSR-042 + Niraparib + Chemotherapy | TIM-3, PD-L1, PARP1/2 | DLTs, AEs, TEAEs, STEAEs, AESIs | ORR, DCR, DOR, PFS, ADA, AUC, Cmax |
NCT04810611 | I | Jun 18, 2021 | Recruiting | LR-MDS, N = 90 | MBG453 ± NIS793 ± Canakinumab | TIM-3, TGF-β, IL-1β | DLTs, AEs, SAEs | BOR, TTP DOR, PFS, ORR |
Anti-TIGIT mAbs
Clinical trial identifier | Phase | Start date | Status | Cancer type (population, N) | Interventions and Combination | Target | Primary Outcome Measures | Secondary Outcome Measures |
---|---|---|---|---|---|---|---|---|
NCT04353830 | I | May 22, 2020 | Complete | Advanced malignancy, N = 34 | IBI939 | TIGIT | AEs, DLTs | AUC, ADA |
NCT04354246 | I | Mar 31, 2020 | Recruiting | Advanced cancer, N = 110 | COM902 | TIGIT | MTD, PK | ORR, CR |
NCT04335253 | I/IIa | Feb 18, 2020 | Completed | Advanced cancer, N = 40 | EOS-448 | TIGIT | RP2D, DLTs | AUC, Cmax |
NCT05394168 | I | Sep 15, 2022 | Not yet recruiting | Advanced/Metastatic Solid Tumor or Lymphoma, N = 20 | HLX53 | TIGIT | MTD, DLTs | ORR, Cmax |
NCT03945253 | I | Aug 5, 2019 | complete | Advanced Solid Tumor, N = 6 | ASP8374 | TIGIT | AEs, DLTs | BOR |
NCT04254107 | I | May 29, 2020 | Recruiting | NSCLC, GC, GEJ, N = 417 | SAE-TGT | TIGIT | AEs, DLTs | ORR, CR |
NCT03563716 | II | Aug 10, 2018 | Active, not recruiting | NSCLC, N = 660 | Tiragolumab + Tecentriq | TIGIT PD-L1 | ORR, PFS | OS, DOR |
NCT04294810 | III | Mar 4, 2020 | Recruiting | NSCLC, N = 136 | Tiragolumab + Atezolizumab | OS, PFS | DOR, ORR | |
NCT05661578 | II | May 4, 2023 | Recruiting | PD-L1-selected Solid Tumor, N = 60 | Tiragolumab + Mosunetuzumab or ± atezolizumab | TIGIT PD-L1 | AEs | AUC, Cmax |
NCT05315713 | I/II | May 10, 2022 | Active, not recruiting | NHL, FL, N = 118 | Tiragolumab + Mosunetuzumab or ± Atezolizumab | TIGIT CD20/CD3; TIGIT PD-L1 | ORR | CR, DOR |
NCT04672369 | Ib | Jun 6, 2021 | Active, not recruiting | Advanced LCA, N = 42 | IBI939 + Sintilimab | TIGIT PD-1 | ORR | OR, PFS, DCR |
NCT04672356 | I | Jan 25, 2021 | Active, not recruiting | Advanced LCA, N = 20 | AEs, RP2D | ORR, DCR | ||
NCT02964013 | I | Dec 13, 2016 | Active, not recruiting | Neoplasms, N = 492 | Vibostolimab + Pembrolizumab | TIGIT PD-1 | DLTs, AEs | ORR, DLTs |
NCT05014815 | II | Nov 16, 2021 | Active, not recruiting | Locally Advanced, Unresectable, or Metastatic NSCLC, NSCLC Stage IV, N = 270 | Ociperlimab + Tislelizumab + Chemotherapy | TIGIT PD-1 | PFS | ORR, DOR, OS |
NCT04952597 | II | Jul 15, 2021 | Active, not recruiting | LS-SCLCr, N = 126 | PFS | CR, DOR, ORR | ||
NCT04047862 | Ib | Aug 26, 2019 | Recruiting | Locally Advanced and Metastatic Solid Tumor, N = 542 | Ociperlimab + Tislelizumab | TIGIT PD-1 | DLTs, ORR, SAE | DOR, DCR |
NCT05267054 | Ib/II | Apr 25, 2022 | Recruiting | rrDLBCL, Refractory DLBCL, N = 80 | Ociperlimab + Tislelizumab/rituximab | TIGIT PD-1/CD20 | AEs, RP2D | ORR, DOR |
NCT05211895 | III | Feb 18, 2022 | Recruiting | NSCLC, N = 860 | Domvanalimab + Durvalumab | TIGIT PD-L1 | PFS, BICR | OS, ORR |
NCT05130177 | II | Mar 16, 2022 | Recruiting | Melanoma, N = 26 | Domvanalimab + Zimberelimab | TIGIT PD-1 | ORR, CR, PR | PFS, OS |
NCT05568095 | III | Nov 21, 2022 | Recruiting | Advanced Upper Gastrointestinal Tract Adenocarcinoma, N = 970 | Domvanalimab + Zimberelimab, Plus Chemotherapy | TIGIT PD-1 | OS | PFS, ORR |
NCT04826393 | I | Mar 9, 2022 | Active, not recruiting | GBM, N = 14 | Domvanalimab + Cemiplimab | TIGIT PD-1 | Tmax, MTD | PFS, OS |
NCT03260322 | I | Sep 8, 2017 | Completed | Advanced Solid Tumor, N = 169 | Domvanalimab + Pembrolizumab | TIGIT PD-1 | DLTs, TEAEs | BOR, ORR |
NCT05289492 | I/II | May 1, 2022 | Recruiting | MM, N = 162 | EOS-448 + iberdomide ± dexamethasone | TIGIT cereblon/GR | SAEs, AEs | PFS, TTR, DCR |
NCT05026606 | II | Oct 1, 2021 | Active, not recruiting | Recurrent-OCCC, Recurrent Platinum-Resistant-FTC, N = 20 | Etigilimab + Nivolumab | TIGIT PD-1 | ORR | irPFS, DCR |
NCT04761198 | Ib/II | Mar 23, 2021 | Active, not recruiting | Solid Tumor Adult, Advanced Solid Tumor, Metastatic Solid Tumor, N = 125 | Etigilimab + Nivolumab | TIGIT PD-1 | ORR | |
NCT04570839 | I/II | Aug 31, 2020 | Active, not recruiting | OV, Solid Tumor, N = 100 | BMS-986207 + COM701 and Nivolumab | TIGIT PVRIG PD-1 | AEs, DLTs | ORR |
NCT04585815 | Ib/II | Nov 10, 2020 | Active, not recruiting | Carcinoma, NSCLC, N = 24 | BMS-986207 + COM701and Nivolumab | TIGIT PD-1 VEGFR Kit PDGFR | DLTs, CR | DR, TTR |
NCT05327530 | II | Aug 17, 2022 | Recruiting | Locally Advanced or Metastatic UC, N = 252 | M6223 + Avelumab | TIGIT PD-L1 | PFS, TEAEs | OS, OR |
Other approaches to targeting LAG-3, TIM-3, and TIGIT for immunotherapy
Clinical trial identifier | Phase | Start date | Status | Cancer type (population, N) | Interventions and combination | Target | Primary outcome measures | Secondary outcome measures |
---|---|---|---|---|---|---|---|---|
NCT03219268 | I | Aug 18, 2017 | Completed | Unresectable or Metastatic Neoplasms, N = 353 | Tebotelimab (MGD013) | LAG-3 PD-1 | TEAEs, etc | AUC, Cmax, etc |
NCT04082364 | II/III | Sep 30, 2019 | Active, not recruiting | GC, GEJC, HER2 + GC, N = 82 | ORR, CR, PR, etc | ADA, etc | ||
NCT04634825 | II | Mar 17, 2021 | Terminated | HNC, HNSCC, N = 62 | ORR, CR, etc | BOR, Cmax, etc | ||
NCT05419388 | I/II | Aug 15, 2022 | Recruiting | Melanoma, N = 80 | RO7247669 | LAG-3 PD-1 | PFS | ORR, DOR, etc |
NCT05645692 | II | Apr 13, 2023 | Recruiting | UC, N = 240 | ORR | OS, DCR, etc | ||
NCT04140500 | I/II | Nov 11, 2019 | Recruiting | Solid tumor, NSCLC, metastatic melanoma, N = 320 | DLTs, ORR, etc | Cmax, AUC, etc | ||
NCT04785820 | II | Jun 25, 2021 | Recruiting | AMESCC, N = 210 | OS | ORR, DCR, etc | ||
NCT05805501 | II | Apr 21, 2023 | Recruiting | RCC, N = 210 | PFS | OS, ORR, etc | ||
NCT05775289 | II | Mar 15, 2023 | Recruiting | NSCLC, N = 180 | PFS, ORR | OS, DOR, etc | ||
NCT04524871 | I/II | Nov 2, 2020 | Recruiting | Advanced LC, N = 400 | ORR | PFS, OS, etc | ||
NCT03440437 | I/II | Apr 16, 2018 | Recruiting | AMC, HNSCC, N = 80 | FS118 | LAG-3 PD-L1 | AUC, CL, etc | Cmax, Tmax, etc |
NCT04618393 | I/II | Mar 11, 2021 | Recruiting | Advanced solid tumors, N = 43 | EMB-02 | LAG-3 PD-1 | SAEs, ORR, etc | AUC, Cmax, etc |
NCT04916119 | I | Jun 29, 2021 | Recruiting | Advanced malignancies, N = 322 | IBI323 | LAG-3 PD-L1 | AEs, etc | ORR, DCR, etc |
NCT03849469 | I | May 29, 2019 | Completed | Melanoma, CESC, PAAD, TNBC, HCC, BLCA, etc, N = 78 | XmAb22841 | LAG-3 CTLA-4 | AEs | – |
NCT05695898 | I/II | Feb 28, 2023 | Recruiting | AM Melanoma, N = 46 | AEs, DLTs, etc | AUC, Cmin, etc | ||
NCT03752177 | Ia/Ib | Nov 22, 2018 | Terminated | Advanced Solid Tumors, N = 12 | LY3415244 | TIM-3 PD-L1 | DLTs | ORR, DOR, etc |
NCT03708328 | I | Oct 15, 2018 | Active, not recruiting | Advanced and/or metastatic solid tumors, N = 134 | Lomvastomig (R07121661) | TIM-3 PD-1 | DLTs, etc | AUC, Cmax, etc |
NCT04785820 | II | Jun 25, 2021 | Recruiting | AMESCC, N = 210 | Lomvastomig (R07121661) | TIM-3 PD-1 | OS | ORR, DOR, etc |
NCT04931654 | I/IIa | Sep 28, 2021 | Recruiting | NSCLC, other AST, N = 81 | AZD7789 | TIM-3 PD-1 | AEs, DLTs, etc | OS, etc |
NCT05216835 | I/II | Mar 18, 2022 | Recruiting | R/R HL, N = 180 | AZD7789 | TIM-3 PD-1 | AEs, DLTs, etc | CRR, ORR, etc |
NCT05357651 | I | Aug 12, 2022 | Recruiting | Advanced solid tumors or lymphoma, N = 100 | LB1410 | TIM-3 PD-1 | TEAEs, SAEs, etc | ORR, DCR, etc |
NCT05005442 | II | Sep 28, 2021 | Recruiting | HMs, N = 180 | MK-7684A | TIGIT PD-1 | DLTs, AEs | ORR, DOR, etc |
NCT04911881 | Ia | Jun 24, 2021 | Completed | Advanced solid tumors, N = 36 | IBI321 | TIGIT PD-1 | DLTs, TRAE | ORR, PFS, etc |
NCT04911894 | I | Jun 21, 2021 | Completed | Advanced solid tumors, N = 16 | AEs, DLTs | DOR, PFS, etc | ||
NCT04995523 | I/II | Sep 14, 2021 | Recruiting | NSCLC, N = 192 | AZD2936 | TIGIT PD-1 | AEs, DLTs, ORR | DCR, DOR, etc |
CTR20220021 | II | Nov 5, 2021 | Recruiting | Advanced solid tumors, N = 30 | ZG005 | TIGIT PD-1 | DLTs, AEs | DCR, DOR, etc |
NCT05025085 | I | Oct 4,2021 | Active, not recruiting | Advanced cancer, N = 70 | AGEN1777 | TIGIT an undisclosed target | DLTs, TEAEs | ADA, CR, etc |