Table 3 Clinical trials on LAG-3

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