Table 3.
Clinical trials on LAG-3
| Target | Drug | Combination agent | Phase | Tumor type | Clinical efficacy | PFS (m) | OS (m) | Safety | Clinical trial | Status |
|---|---|---|---|---|---|---|---|---|---|---|
| LAG-3 | BMS 986,016(Relatlimab) | Nivolumab | Phase 2/3 | Melanoma | Researchers provided data on PFS*, ORR of the Relatlimab–Nivolumab group and the Nivolumab group was 43% and 33% | 10.12 for group: Relatlimab + Nivolumab, and 4.63 for group: Nivolumab* | NR for group: Relatlimab + Nivolumab, and 34 for group: Nivolumab | Serious adverse events were 108/355 for Group A: Relatlimab + Nivolumab, and 119/359 for Nivolumab | NCT03470922 (RELATIVITY-047) | Active, not recruiting |
| Nivolumab | Phase 1 | Cancer | – | – | – | – | NCT02966548 | Active, not recruiting | ||
| BMS-936558 | Phase 1 | Hematologic neoplasms | – | – | – | – | NCT02061761 | Active, not recruiting | ||
| Nivolumab | Phase 2 | Melanoma | – | – | – | – | NCT03743766 | Recruiting | ||
| Nivolumab, BMS-986213 | Phase 1 | Neoplasms by site | – | – | – | – | NCT01968109 | Active, not recruiting | ||
| Phase 2 | ||||||||||
| Nivolumab | Phase 2 | Metastatic uveal melanoma | – | – | – | – | NCT04552223 | Recruiting | ||
| Nivolumab | Phase 1 | Glioblastoma | – | – | – | – | NCT03493932 | Active, not recruiting | ||
| Nivolumab | Phase 2 | Chordoma, locally advanced chordoma, metastatic chordoma, unresectable chordoma | – | – | – | – | NCT03623854 | Recruiting | ||
| Anti-PD-1 | Phase 1 | Glioblastoma | – | – | – | – | NCT02658981 | Active, not recruiting | ||
| Anti-CD137 | Gliosarcoma, recurrent brain neoplasm | |||||||||
| Elotuzumab, pomalidomide, dexamethasone | Phase 1 | Multiple myeloma | – | – | – | – | NCT04150965 | Recruiting | ||
| Azacitidine Injection | Phase 2 | Acute myeloid leukemia | – | – | – | – | NCT04913922 | Recruiting | ||
| Nivolumab | Phase 3 | Melanoma | – | – | – | – | NCT05002569 | Not yet recruiting | ||
| Nivolumab | Phase 2 | Hepatocellular carcinoma, hepatoma | – | – | – | – | NCT04567615 | Recruiting | ||
| Nivolumab | Phase 1 | Various advanced cancers | ORR 0 for HPV-positive SCCHN * | 3.81 | 8.84 | Serious adverse events included one case for angina pectoris, pathological fracture, pleural effusion, pulmonary hemorrhage, stridor each, two cases for malignant neoplasm, and three cases for dyspnea* | NCT02488759 | Active, not recruiting | ||
| Nivolumab | Phase 1 | Advanced cancer | – | – | – | – | NCT03459222 | Recruiting | ||
| Nivolumab | Phase 2 | Advanced cancer | – | – | – | – | NCT02996110 | Recruiting | ||
| Nivolumab | Phase 1 | Hepatocellular carcinoma | – | – | – | – | NCT04658147 | Recruiting | ||
| Nivolumab + Ipilimumab | Phase 2 | HNSCC | – | – | – | – | NCT04326257 | Recruiting | ||
| Nivolumab | Phase 2 | MSS colorectal adenocarcinomas | – | – | – | – | NCT03642067 | Recruiting | ||
| Nivolumab | Phase 2 | Refractory MSI-H solid tumors prior to PD-(L) 1 therapy | – | – | – | – | NCT03607890 | Recruiting | ||
| Nivolumab | Phase 2 | HNSCC | – | – | – | – | NCT04080804 | Recruiting | ||
| Nivolumab | Phase 2 | Advanced gastric cancer | – | – | – | – | NCT02935634 | Active, not recruiting | ||
| Nivolumab, Carboplatin, Paclitaxel, Radiation | Phase 1 | Gastric cancer, esophageal cancer, gastroesophageal cancer | – | – | – | – | NCT03044613 | Active, not recruiting | ||
| IMP321 (Eftilagimod Alpha) | Gemcitabine | Phase 1 | Pancreatic neoplasms | – | – | – | – | NCT00732082 | Terminated | |
| Pembrolizumab | Phase 1 | Stage IV melanoma, stage III melanoma | 1/18 CR | – | – | No DLTs reported* | NCT02676869 | Completed | ||
| Paclitaxel, Placebo | Phase 2 | Adenocarcinoma breast stage IV | – | – | – | – | NCT02614833 | Active, not recruiting | ||
| – | Phase 1 | Advanced RCC | 7 of 8 patients treated with the higher doses of IM321 underwent SD at three months. 3 of 11 in the lower dose group did | – | – | No clinically significant local or systemic treatment-related adverse events were recorded. Along with the 195 adverse events, 20 (10%) were reported to be related to IMP321 and were grade 1 local reactions* | NCT00351949 (P003) | Completed | ||
| Avelumab | Phase 1 | Solid tumors, peritoneal carcinomatosis | ORR 17% and DCR 33% with 1/6 PR, 1/6 SD, and 4/6 PD | – | – | No DLTs reported* | NCT03252938 | Recruiting | ||
| Paclitaxel | Phase 1 | Metastatic breast cancer | ORR 50% and 1/10 PD | – | – | Six grade 3 adverse events were recorded, including asthenia (3 cases), neuropathy, allergic reaction, and neutropenia* | NCT00349934 | Completed | ||
| Pembrolizumab | Phase 2 | NSCLC, HNSCC | ORR 47%* and DCR 82% with 8/17 PR and 6/17 SD | – | – | Most common toxicities included cough (31%), fatigue (19%), and diarrhea (15%) | NCT03625323 | Recruiting | ||
| Pembrolizumab | Phase 2 | HNSCC | – | – | – | – | NCT04811027 | Not yet recruiting | ||
| Paclitaxel | Phase 1 | Metastatic breast cancer | – | – | – | – | NCT04252768 | Not yet recruiting | ||
| Immunological peptides and immunological adjuvants | Phase 1 | Melanoma | – | – | – | – | NCT00365937 | Terminated | ||
| HLA-A2 peptides | Phase 2 | |||||||||
| Montanide ISA-51 | ||||||||||
| Melan-A VLP vaccine, cyclophosphamide, fludarabine phosphate | Phase 1 | Melanoma | – | – | – | Grade 3–4 treatment-related adverse events included anemia (16.6%), leucopenia (100%), thrombocytopenia (33%), febrile neutropenia (grade 3) (50%), CD4 lymphopenia (≥ grade 3) (100%) * | NCT00324623 | Completed | ||
| Sym022 | – | Phase 1 | Metastatic cancer, solid tumor, lymphoma | 33.3% SD in group: Dose Level 3 | – | – | Serious adverse events were 1/3 in Dose Level 3(chest pain) and 2/6 in Dose Level 4 (gastrointestinal hemorrhage, sepsis, lipase increased, and tumor pain) * | NCT03489369 | Completed | |
| Sym021 | Phase 1 | Metastatic cancer, solid tumor | – | – | – | – | NCT04641871 | Active, not recruiting | ||
| Sym021 | Phase 1 | Metastatic cancer, solid tumor, lymphoma | – | – | – | – | NCT03311412 | Recruiting | ||
| INCAGN02385 | – | Phase 1 | Cervical cancer, MSI-high endometrial cancer | – | – | – | – | NCT03538028 | Completed | |
| INCAGN02390, INCMGA00012 | Phase 1/2 | Melanoma | – | – | – | – | NCT04370704 | Recruiting | ||
| REGN3767 | – | Early Phase 1 | Large B cell lymphoma, DLBCL | – | – | – | – | NCT04566978 | Recruiting | |
| Cemiplimab | Phase 1 | Malignancies |
Monotherapy group: ORR 0% and DCR 48% with 12 SD Combination group: ORR 5% and DCR was 31% with 2 PR and 11 SD 2/12 PR and 6 SD in the group crossed over from monotherapy to the combination |
– | – | 1/67 DLT in the combination group (G4 CK elevation + G3 myasthenic syndrome + G1 elevation of troponin* | NCT03005782 | Recruiting | ||
| Cemiplimab | Phase 1/2 | Metastatic solid tumor | – | – | – | – | NCT04706715 | Not yet recruiting | ||
| RO7247669 | – | Phase 1 | Solid tumors, metastatic melanoma, NSCLC, esophageal squamous cell carcinoma | – | – | – | – | NCT04140500 | Recruiting | |
| RO7121661 | Phase 2 | Advanced or metastatic esophageal squamous cell carcinoma | – | – | – | – | NCT04785820 | Recruiting | ||
| Atezolizumab | Phase 1 | Advanced liver cancers | – | – | – | – | NCT04524871 | Recruiting | ||
| BI 754,091 | Anti-PD-1 | Phase1 | Advanced or metastatic solid tumors | – | – | – | 21/321 DLTs, particularly infusion-related reactions (n = 6). Serious AEs: 77/321 (27%): pleural effusion (n = 6), deep venous thrombosis (n = 4), cardiac tamponade (n = 1), and acute kidney injury (n = 1) | NCT03156114 | Active, not recruiting | |
| Anti-PD-1 | Phase1 | NCT03433898 | Active, not recruiting | |||||||
| Anti-PD-1 | Phase1 | NCT03780725 | Terminated | |||||||
| Anti-PD-1 | Phase2 | NCT03697304 | Active, not recruiting | |||||||
| EMB-02 | – | Phase 1 | Advanced solid tumors | NCT04618393 | Recruiting | |||||
| LAG525 | PDR001 | Phase 2 | SCLC, gastric adenocarcinoma, esophageal adenocarcinoma, castration-resistant prostate adenocarcinoma, soft tissue sarcoma, ovarian adenocarcinoma, advanced well-differentiated neuroendocrine tumors | ORR 9.3%, DCR for neuroendocrine tumors (86%), diffuse large B cell lymphoma (43%), and small-cell lung cancer (27%)* | 2.8 | – | 11/72 patients had grade 3 or 4 AEs including dyspnea, fatigue, and poor appetite | NCT03365791 | Completed | |
| DLBCL | ||||||||||
| Spartalizumab | Phase 2 | Triple-negative breast cancer | ORR for LAG525 + Spartalizumab (5.0), LAG525 + Spartalizumab + Carboplatin (32.4), LAG525 + Carboplatin (17.6)* | LAG525 + Spartalizumab (1.4), LAG525 + Spartalizumab + Carboplatin (4.3), LAG525 + Carboplatin (3.0) | – | Serious adverse events for LAG525 + Spartalizumab (6/19), LAG525 + Spartalizumab + Carboplatin (12/34), LAG525 + Carboplatin (14/34) | NCT03499899 | Completed | ||
| PDR001 | Phase 1 | Advanced solid tumors |
11/121 patients in the combination group achieved PR 1 patient had a CR |
– | – | DLTs occurred in 4/121 patients including grade 3 and 4 pneumonitis, acute kidney injury, and autoimmune hepatitis* | NCT02460224 | Completed | ||
| Spartalizumab | Phase 1 | TNBC | – | – | – | – | NCT03742349 | Recruiting | ||
| Spartalizumab | Phase 2 | Melanoma | – | – | – | – | NCT03484923 | Recruiting | ||
| MGD013 | Alone or in combination with margetuximab (for patients who had expression of HER2 on their tumors) | Phase1 | Advanced or metastatic solid or hematologic malignancies |
Dose escalation (n = 29): ORR 10% and DCR 55% with 3 confirmed PR, 1 unconfirmed PR, and 13 SD Expansion cohort (n = 41): ORR 7%, DCR 59% with 3 PR, and 21 SD |
– | – | 2/207 DLTs: immune-mediated hepatitis and increased lipase* | NCT03219268 | Active, not recruiting | |
| FS118 | Phase1 | Advanced solid tumors | – | – | – | – | NCT03440437 | Recruiting |
*Primary endpoint; NSCLC, non-small-cell lung cancer; SCLC, small-cell lung cancer; HNSCC, head and neck squamous cell carcinoma; MSS, microsatellite stable; UC, urothelial cancer; TNBC, triple-negative breast cancer; DLBCL, diffuse large B cell lymphoma; MSI, microsatellite instability