LAG-3 as a Potent Target for Novel Anticancer Therapies of a Wide Range of Tumors
Abstract
:1. Introduction
2. LAG-3 Expression
3. LAG-3 in Neoplasms
3.1. Brain Tumors
3.2. Head and Neck Tumors
3.3. Endocrine Tumors
3.4. Lung Tumors
3.5. Abdominal Tumors
3.6. Uro-Genital Tumors
3.7. Breast Tumors
3.8. Skin Tumors
3.9. Lymphoid Tumors
4. Anti-LAG-3 Antibody-Based Therapies
5. Anti-LAG-3 Cell-Based Therapies
6. Experimental Medicine Involving LAG-3 Clinical Trials
6.1. Anti-LAG-3 Monoclonal Antibodies
6.2. Anti-LAG-3 Bispecifics
6.3. Soluble LAG-3–Ig Fusion Proteins
7. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Identifier | Patients Number | Recruitment Status | Condition or Disease | Target | Therapy Protocol | Short Description |
---|---|---|---|---|---|---|
NCT01968109 | 1499 | Active, not recruiting | Neoplasms by Site | LAG-3 PD-1 | Biological: Relatlimab Biological: Nivolumab Biological: BMS-986213 | Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination with Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors |
NCT03662659 | 274 | Active, not recruiting | Gastric Cancer Cancer of the Stomach Esophagogastric Junction | LAG-3 PD-1 | Biological: BMS-986213 Biological: Nivolumab Drug: XELOX Drug: FOLFOX Drug: SOX | Relatlimab and Nivolumab in Combination with Chemotherapy Versus Nivolumab in Combination with Chemotherapy as First-Line Treatment in Patients with Gastric or Gastroesophageal Junction Adenocarcinoma |
NCT02061761 | 107 | Active, not recruiting | Hematologic Neoplasms | LAG-3 PD-1 | Biological: BMS-986016 Biological: BMS-936558 | Anti-LAG-3 Monoclonal Antibody (Relatlimab, BMS-986016) Administered Alone and in Combination with Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Relapsed or Refractory B-Cell Malignancies |
NCT03493932 | 20 | Active, not recruiting | Glioblastoma | LAG-3 | Drug: Nivolumab Drug: BMS-986016 | Nivolumab, together with an anti-LAG-3 antibody BMS-986016 in Patients with Glioblastoma |
NCT04150965 | 104 | Active, Recruiting | Multiple Myeloma Relapsed Refractory Multiple Myeloma | LAG-3 TIGIT | Drug: Elotuzumab, pomalidomide, dexamethasone Drug: Anti-LAG-3 Drug: Anti-LAG-3 + Pomalidimide + Dexamethasone Drug: Anti-TIGIT Drug: Anti-TIGIT + Pomalidimide + Dexamethasone | Combination Immuno-Oncology Drugs Elotuzumab, Anti-LAG-3 (BMS-986016) and Anti-TIGIT (BMS-986207) in Patients with Multiple Myeloma |
NCT03044613 | 32 | Active, not recruiting | Gastric Cancer Esophageal Cancer Gastroesophageal Cancer | LAG-3 PD-1 | Drug: Nivolumab Drug: Relatlimab Drug: Carboplatin Drug: Paclitaxel Radiation: Radiation | Nivolumab or Nivolumab/Relatlimab Prior to Concurrent Chemoradiation in Patients with Operable Stage II/III Esophageal/ Gastroesophageal Junction Cancer |
NCT04080804 | 60 | Active, Recruting | Head and Neck Squamous Cell | LAG-3 PD-1 CTLA-4 | Drug: Nivolumab Drug: Relatlimab | Anti-PD1 (Nivolumab) Administered Alone or in Combination with Anti-LAG3 (Relatlimab) or Anti-CTLA4 (Ipilimumab) in Resectable Head and Neck Cancer |
NCT03459222 | 255 | Active, Recruiting | Advanced Cancer | LAG-3 PD-1 CTLA-4 | Biological: Relatlimab Biological: Nivolumab Drug: BMS-986205 Biological: Ipilimumab | Relatlimab (Anti-LAG-3 Monoclonal Antibody) Administered in Combination with Both Nivolumab (Anti-PD-1 Monoclonal Antibody) and BMS-986205 (IDO1 Inhibitor) or in Combination with Both Nivolumab and Ipilimumab (Anti-CTLA-4 Monoclonal Antibody) in Advanced Malignant Tumours |
NCT03005782 | 669 | Active, Recruting | Malignancies | LAG-3 PD-1 | Drug: REGN3767 Drug: cemiplimab | REGN3767 (Anti-LAG-3 mAb) Administered Alone or in Combination with REGN2810 (Anti-PD-1 mAb) in Patients with Advanced Malignancies |
NCT04566978 | 20 | Active Recruiting | Large B-cell Lymphoma DLBCL | LAG-3 | Drug: 89Zr-DFO-REGN3767 Diagnostic Test: PET/CT | 89Zr-DFO-REGN3767 Anti LAG-3 Antibody Positron Emission Tomography in Patients with Relapsed/Refractory DLBCL |
NCT03489369 | 15 | Completed, Phase 1 | Metastatic Cancer Solid Tumor Lymphoma | LAG-3 | Experimental: Sym022 | Antineoplastic Activity of Sym022 (Anti-LAG-3) in Patients with Advanced Solid Tumor Malignancies or Lymphomas |
NCT03311412 | 91 | Completed, Phase 1 | Metastatic Cancer Solid Tumor Lymphoma | LAG-3, PD-1, TIM-3 | Drug: Sym021 Drug: Sym022 Drug: Sym023 | Activity of Sym021 (Anti-PD-1) as Monotherapy, in Combination with Either Sym022 (Anti-LAG-3) or Sym023 (Anti-TIM-3), and in Combination with Both Sym022 and Sym023 in Patients with Advanced Solid Tumor Malignancies or Lymphomas |
NCT04641871 | 100 | Active Recruiting | Metastatic Cancer Solid Tumour | LAG-3 PD-1 TIM-3 | Drug: Sym021 Drug: Sym022 Drug: Sym023 Drug: Irinotecan Hydrochloride | Sym021 (Anti-PD 1) in Combination with Either Sym022 (Anti-LAG-3) or Sym023 (Anti-TIM-3) or Sym023 and Irinotecan in Patients with Recurrent Advanced Biliary Tract Carcinomas |
NCT03250832 | 111 | Active, not recruiting | Neoplasms | LAG-3 PD-1 | Drug: TSR-033 Drug: Dostarlimab Drug: mFOLFOX6 Drug: FOLFIRI Drug: Bevacizumab | TSR-033, an Anti-LAG-3 Monoclonal Antibody, Alone and in Combination with an Anti-PD-1 in Patients with Advanced Solid Tumours |
NCT03499899 | 88 | Completed | Triple-negative Breast Cancer | LAG-3 PD-1 | Drug: LAG525 Drug: spartalizumab Drug: carboplatin | LAG525 in Combination with Spartalizumab, or with Spartalizumab and Carboplatin, or with Carboplatin, in Patients with Advanced Triple-negative Breast Cancer |
NCT02460224 | 490 | Completed | Advanced Solid Tumours | LAG-3 PD-1 | Drug: LAG525 Drug: PDR001 | LAG525 Single Agent and in Combination with PDR001 Administered to Patients with Advanced Malignancies |
NCT03484923 | 196 | Active, not recruiting | Melanoma | LAG-3 PD-1 MET IL-1β CDK4/6 | Drug: Spartalizumab Drug: LAG525 Drug: Capmatinib Drug: Canakinumab Drug: Ribociclib | Spartalizumab (PDR001) Combinations in Previously Treated Unresectable or Metastatic Melanoma |
NCT05064059 | 432 | Active, recruiting | Colorectal Cancer | LAG-3 PD-1 | Biological: favezelimab/pembrolizumab Drug: regorafenib Drug: TAS-102 | Favezelimab/Pembrolizumab (MK-4280A) in participants with metastatic colorectal cancer |
NCT03598608 | 154 | Active, recruiting | Hodgkin Disease Lymphoma, Non-Hodgkin Lymphoma, B-Cell | LAG-3 PD-1 | Biological: pembrolizumab Biological: Favezelimab | Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants with Hematologic Malignancies |
Identifier | Patients Number | Recruitment Status | Condition or Disease | Target Antigen | Therapy Protocol | Short Description |
---|---|---|---|---|---|---|
NCT03219268 | 353 | Active, not recruiting | Advanced Solid Tumors Hematologic Neoplasms Ovarian Cancer HER2-positive Advanced Solid Tumors Non-Small Cell Lung Cancer Small-cell Lung Cancer Squamous Cell Carcinoma of Head and Neck Cholangiocarcinoma Cervical Cancer TNBC-Triple-Negative Breast Cancer | LAG-3 PD-1 | Biological: tebotelimab Biological: margetuximab | MGD013, A Bispecific DART® Protein Binding PD-1 and LAG-3 in Patients with Unresectable or Metastatic Neoplasms |
NCT04140500 | 320 | Active, Recruiting | Solid Tumors Metastatic Melanoma Non-small Cell Lung Cancer Esophageal Squamous Cell Carcinoma | LAG-3 PD-1 | Drug: RO7247669 | RO7247669, a PD1-LAG3 Bispecific Antibody, in Patients with Advanced and/or Metastatic Solid Tumours |
NCT03440437 | 80 | Active, Recruiting | Advanced Cancer Metastatic Cancer Squamous Cell Carcinoma of Head and Neck | LAG-3 PD-1 | Drug: FS118 | FS118, a LAG-3/PD-L1 Bispecific Antibody, in Patients with Advanced Malignancies |
NCT04618393 | 43 | Active, Recruting | Advanced Solid Tumor | LAG-3 PD-1 | Biological: EMB-02 | EMB-02, a Bi-specific Antibody Against PD-1 and LAG-3, in Patients with Advanced Solid Tumors |
NCT04916119 | 322 | Active Recruiting | Advanced Malignancies | LAG-3 PD-1 | Drug: IBI323 | IBI323(anti-LAG-3/PD-L1) or in combination with chemotherapy in participants with advanced malignancies |
NCT03849469 | 242 | Active Recruiting | Solid tumors | LAG-3 CTLA-4 | Biological: XmAb®22841 Biological: Pembrolizumab (Keytruda®) | XmAb22841 monotherapy and in combination with pembrolizumab in Patients with Solid tumors |
Identifier | Patients Number | Recruitment Status | Condition or Disease | Target Antigen | Therapy Protocol | Short Description |
---|---|---|---|---|---|---|
NCT00349934 | 33 | Completed, Phase 1 | Metastatic Breast Cancer | LAG-3 | Biological: IMP321 | IMP321 in Metastatic Breast Carcinoma Patients Receiving First-line Paclitaxel |
NCT02614833 | 242 | Completed | Adenocarcinoma Breast Stage IV | LAG-3 | Biological: IMP321 (eftilagimod alpha) Drug: Placebo Drug: Paclitaxel | Study in Hormone Receptor-positive Metastatic Breast Carcinoma Patients Receiving IMP321 (LAG-3Ig Fusion Protein) or Placebo as Adjunctive to a Standard Chemotherapy Treatment Regimen of Paclitaxel |
NCT00351949 | 24 | Completed | Stage IV Renal Cell Carcinoma | LAG-3 | Biological: IMP321 | IMP321 in Advanced or Metastatic Renal Cell Carcinoma Patients |
NCT03252938 | 45 | Active, Recruiting | Solid Tumors Peritoneal Carcinomatosis | LAG-3 | Drug: IMP321 Drug: Avelumab | MP321 (LAG-3Ig Fusion Protein) in Patients with Advanced Stage Solid Tumor Entities |
NCT00351949 | 24 | Completed | Stage IV Renal Cell Carcinoma | LAG-3 | Biological: IMP321 | IMP321 in Patients with Metastatic Renal Cell Carcinoma (MRCC) |
NCT02676869 | 24 | Completed | Stage IV Melanoma Stage III Melanoma | LAG-3 PD-1 | Drug: IMP321 (eftilagimod alpha) Drug: Pembrolizumab | MP321 in Patients in Combination with Pembrolizumab in Patients with Unresectable or Metastatic Melanoma |
NCT01968109 | 1499 | Active, not recruiting | Neoplasms by Site | LAG-3 PD-1 | Biological: Relatlimab Biological: Nivolumab Biological: BMS-986213 | Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination with Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors |
NCT03044613 | 32 | Active, not recruiting | Gastric Cancer Esophageal Cancer Gastroesophageal Cancer | LAG-3 PD-1 | Drug: Nivolumab Drug: Relatlimab Drug: Carboplatin Drug: Paclitaxel Radiation: Radiation | Nivolumab or Nivolumab/Relatlimab Prior to Concurrent Chemoradiation in Patients with Operable Stage II/III Esophageal/ Gastroesophageal Junction Cancer |
NCT04370704 | 144 | Active, Recruiting | Melanoma | LAG-3 PD-1 TIM-3 | Drug: INCAGN02385 Drug: INCAGN02390 Drug: INCMGA00012. | Combination Therapy with INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants with Select Advanced Malignancies |
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Sauer, N.; Szlasa, W.; Jonderko, L.; Oślizło, M.; Kunachowicz, D.; Kulbacka, J.; Karłowicz-Bodalska, K. LAG-3 as a Potent Target for Novel Anticancer Therapies of a Wide Range of Tumors. Int. J. Mol. Sci. 2022, 23, 9958. https://doi.org/10.3390/ijms23179958
Sauer N, Szlasa W, Jonderko L, Oślizło M, Kunachowicz D, Kulbacka J, Karłowicz-Bodalska K. LAG-3 as a Potent Target for Novel Anticancer Therapies of a Wide Range of Tumors. International Journal of Molecular Sciences. 2022; 23(17):9958. https://doi.org/10.3390/ijms23179958
Chicago/Turabian StyleSauer, Natalia, Wojciech Szlasa, Laura Jonderko, Małgorzata Oślizło, Dominika Kunachowicz, Julita Kulbacka, and Katarzyna Karłowicz-Bodalska. 2022. "LAG-3 as a Potent Target for Novel Anticancer Therapies of a Wide Range of Tumors" International Journal of Molecular Sciences 23, no. 17: 9958. https://doi.org/10.3390/ijms23179958