Table 5 Clinical trials on TIM-3, BTLA, CD47, B7-H3, B7-H4, CD70, and TIGIT

TIM-3

Sym023

–

Phase 1

Metastatic Cancer Solid Tumor Lymphoma

3 patients were reported SD > 16 weeks, 7 were reported SD ≤ 16 weeks. ORR not reported

–

–

Researchers reported one case of immune-mediated arthritis for Sym023 0.1 mg/kg, one case of lipase increased and pathological fracture each for 10.0 mg/kg, and one case of back pain plus spinal cord compression for 20.0 mg/kg*

NCT03489343

Completed

Sym021 Sym022

Phase 1

Metastatic Cancer Solid Tumor

–

–

–

–

NCT04641871

Recruiting

Sym021 Sym022

Phase 1

Metastatic Cancer Solid Tumor Lymphoma

–

–

–

–

NCT03311412

Completed

MBG453 (Sabatolimab)

Venetoclax Azacitidine

Phase 2

Acute Myeloid Leukemia

–

–

–

–

NCT04150029

Recruiting

Azacitidine

Phase 3

MDS Leukemia Myelomonocytic Chronic

–

–

–

–

NCT04266301

Active, not recruiting

Hypomethylating agents

Phase 2

MDS

–

–

–

–

NCT03946670

Active, not recruiting

HDM201 Venetoclax

Phase 1

AML High-risk MDS

–

–

–

–

NCT03940352

Recruiting

PDR001 Decitabine

Phase 1 Phase 2

Advanced Malignancies

ORR in the monotherapy group was 0% and DCR was 29% with 25/87 SD*

ORR in the combination group was 5% and DCR was 44% with 4/86 PR and 34/86 SD*

–

–

One DLT in combination cohort (grade 4 MG)*

11% developed grade 3 or 4 AEs in the combination cohort*

NCT02608268

Active, not recruiting

–

Phase 1

GBM

–

–

–

–

NCT03961971

Recruiting

Azacitidine Decitabine INQOVI (oral decitabine)

Phase 2

MDS

–

–

–

–

NCT04878432

Recruiting

Sabatolimab Azacitidine

Phase 1 Phase 2

Acute Myeloid Leukemia

–

–

–

–

NCT04623216

Recruiting

NIS793 canakinumab

Phase 1

MDS

–

–

–

–

NCT04810611

Recruiting

Sabatolimab, azacitidine, venetoclax

Phase 2

MDS

–

–

–

–

NCT04812548

Recruiting

TSR-022

TSR-042

Phase 2

Adult Primary Liver Cancer Advanced Adult Primary Liver Cancer Localized Unresectable Adult Primary Liver Cancer

–

–

–

–

NCT03680508

Recruiting

TSR-042

Phase 2

Melanoma Stage III Melanoma Stage IV

–

–

–

–

NCT04139902

Recruiting

–

Phase1

Advanced solid tumors

–

–

–

–

NCT02817633

Recruiting

RO7121661

–

Phase 1

Solid Tumors Metastatic Melanoma NSCLC SCLC ESCC

–

–

–

–

NCT03708328

Active, not recruiting

RO7247669 Nivolumab

Phase 2

Advanced or Metastatic ESCC

–

–

–

–

NCT04785820

Recruiting

LY3321367

LY3300054

Phase 1

Solid Tumor

In monotherapy expansion cohort, outcomes varied: anti-PD-1/L1 refractory patients [N = 23, ORR 0%, DCR 35%, PFS 1.9 months] versus anti-PD-1/L1 responders (N = 14, ORR 7%, DCR 50%, PFS 7.3 months). In combination expansion cohorts (N = 91), ORR and DCR were 4% and 42%

1.9, 7.3(detailed in Clinical efficacy)

–

No DLTs were observed*, treatment-related adverse events (≥ 2 patients) included pruritus, rash, fatigue, anorexia, and infusion-related reactions

NCT03099109

Active, not recruiting

LY3300054 Ramucirumab Abemaciclib Merestinib

Phase 1

Solid Tumor MSI-H Solid Tumors Cutaneous Melanoma Pancreatic Cancer Breast Cancer (HR + HER2-)

–

–

–

DLTs associated with hepatotoxicity were observed in 3 of 4 patients in the abemaciclib lead-in cohorts. No DLTs or grade 3 or 4 hepatotoxicity were reported in the concurrent abemaciclib arm*

NCT02791334

Active, not recruiting

BTLA

JS004

–

Phase 1

Advanced Solid Tumors

–

–

–

–

NCT04773951

Recruiting

Toripalimab

Phase 1 Phase 2

Advanced Lung Cancer

–

–

–

–

NCT05000684

Recruiting

–

Phase 1 Phase 2

HNSCC Nasopharyngeal Carcinoma

–

–

–

–

NCT04929080

Recruiting

–

Phase 1

Recurrent/Refractory Malignant Lymphoma

–

–

–

–

NCT04477772

Recruiting

–

Phase 1

Advanced Solid Tumor

–

–

–

–

NCT04278859

Unknown

Toripalimab

Phase 1

Advanced Unresectable Solid Tumor Metastatic Solid Tumor

–

–

–

–

NCT04137900

Recruiting

Toripalimab

Phase 1

Advanced Unresectable Solid Tumor Metastatic Solid Tumor

–

–

–

–

NCT04137900

Recruiting

CD47

Magrolimab (Hu5F9-G4)

Phase 1

Solid tumors

ORR ~ 5%

DCR 19% with 2/43 PR (ovarian and fallopian tube cancers) and 6/43 SD (CRC)*

–

–

AEs occurred with higher doses. These included constitutional symptoms (50%), headache (34%), anemia (39%), and lymphopenia (28%) *

NCT02216409

Completed

Rituximab Gemcitabine Oxaliplatin

Phase 1 Phase 2

Non-Hodgkin Lymphoma

CRR 21%

ORR 49% with 16/75 CR and 21/75 PR

–

–

DLTs 4% (no specifics provided) *

NCT02953509

Active, not recruiting

Venetoclax Azacitidine Cytarabine Daunorubicin Idarubicin Steroidal Eye Drops

Phase 3

AML

–

–

–

–

NCT04778397

Recruiting

AK117

–

Phase 1

Neoplasms Malignant

–

–

–

–

NCT04728334

Recruiting

Azacitidine

Phase 1 Phase 2

Myelodysplastic Syndrome

–

–

–

–

NCT04900350

Recruiting

Azacitidine

Phase 1 Phase 2

Acute Myeloid Leukemia

–

–

–

–

NCT04980885

Recruiting

Phase 1

Neoplasms Malignant

–

–

–

–

NCT04349969

Not yet recruiting

AK112 Nab-paclitaxel paclitaxel

Phase 2

Metastatic Triple-negative Breast Cancer Locally Advanced Triple-negative Breast Cancer

–

–

–

–

NCT05227664

Recruiting

Capecitabine tablets Oxaliplatin Cisplatin Paclitaxel Irinotecan Docetaxel 5-FU AK104

Phase 1 Phase 2

Advanced Malignant Tumors

–

–

–

–

NCT05235542

Not yet recruiting

TTI-622

–

Phase 1

Relapsed or refractory lymphomas

1 patient (DLBCL) with 5 prior lines of therapy achieved a PR by week 8 and a CR by week 36

–

–

No DLTs*

NCT03530683 (TTI-622–01)

Recruiting

RRx-001

Nivolumab

Phase 1

Advanced solid malignancies or lymphomas

ORR 25%, DCR 67% with 3/12 PR, 5/12 SD, and 3/12 PD

–

–

No DLTs reported

1 patient discontinued therapy due to pneumonitis*

NCT02518958 (PRIMETIME)

Completed

B7-H3

MGC018

MGA012

Phase 1 Phase 2

Advanced Solid Tumor, Adult Metastatic Castrate Resistant Prostate Cancer NSCLC TNBC HNSCC Melanoma Prostate Cancer

ORR 0% and DCR 15% with 3/20 SD

–

–

1 DLT: grade 4 neutropenia

3 serious AEs: pneumonitis, gastroenteritis, stasis dermatitis*

NCT03729596

Recruiting

B7-H3 CAR-T

Temozolomide

Phase 1

Recurrent GBM Refractory GBM

–

–

–

–

NCT04385173

Unknown

Temozolomide

Phase 1 Phase 2

Recurrent GBM Refractory GBM

–

–

–

–

NCT04077866

Recruiting

–

Phase 1

Lung Cancer Immunotherapy CAR-T Cell

–

–

–

–

NCT03198052

Recruiting

Fludarabine Cyclophosphamide

Phase 1

Epithelial Ovarian Cancer

–

–

–

–

NCT04670068

Recruiting

–

Early Phase 1

Osteosarcoma Neuroblastoma Gastric Cancer Lung Cancer

–

–

–

–

NCT04864821

Not yet recruiting

–

Phase 1 Phase 2

Solid Tumor

–

–

–

–

NCT04432649

Recruiting

GD2, PSMA CAR-T cells

Phase 1 Phase 2

Neuroblastoma

–

–

–

–

NCT04637503

Recruiting

Enoblituzumab (MGA271)

–

Phase 1

Neuroblastoma Rhabdomyosarcoma Osteosarcoma Ewing Sarcoma Wilms Tumor Desmoplastic Small Round Cell Tumor

–

–

–

–

NCT02982941

Completed

Ipilimumab

Phase 1

Melanoma NSCLC

–

–

–

–

NCT02381314

Completed

–

Phase 2

Prostate Cancer

31% of patients had a more than 10% decline in PSA before post-prostatectomy, and an altered Gleason score was observed*

–

–

3 cases of serious adverse events*, including ascites, pericardial effusion, cardiac disorders, atrial fibrillation, pericarditis, myocarditis, and infusion-related reaction

NCT02923180

Active, not recruiting

Retifanlimab Tebotelimab

Phase 2

Head and Neck Cancer Head and Neck Neoplasms HNSCC

–

–

–

–

NCT04634825

Recruiting

IP FT516 IL-2

Phase 1

Ovarian Cancer Fallopian Tube Adenocarcinoma Primary Peritoneal Cavity Cancer

–

–

–

–

NCT04630769

Completed

Pembrolizumab MGA012

Phase 1

Melanoma Head and Neck Cancer NSCLC UC

ORR 33.3% for patients with CPI-naïve HNSCC, and 35.7% for patients with CPI-naïve NSCLC

–

–

Treatment-related adverse events occurred in 116 patients (87.2%) and were grade ≥ 3 in 28.6%*

NCT02475213

Completed

B7-H4

FPA150

–

Phase 1

B7-H4 positive solid malignancies

ORR 3% and DCR 38% with 1/29 PR and 10/29 SD

–

–

No DLTs or grade 4/5 toxicities were reported

NCT03514121

Completed

CD70

SGN-CD70A

–

Phase 1

CD70-positive metastatic RCC

One patient in the 50-μg/kg cohort achieved a PR (6%), and 13 out of 18 patients (72%) had SD. Thus, the overall disease control rate was 78%, and the estimated median PFS was 3.5 months

3.5 months

–

Grade 3 TEAEs were thrombocytopenia (22%), anemia (17%), neutropenia (17%), and dehydration (11%)*

NCT02216890

Completed

Cusatuzumab

Azacitidine and Venetoclax

Phase 1

AML

–

–

–

–

NCT04150887

Active, not recruiting

TIGIT

Tiragolumab

Atezolizumab

Phase 2

NSCLC

ORR 31.3% in experimental group vs 16.4% in the control group*

5.4 months vs 3.6 months*

–

14 (21%) patients receiving combination therapy and 12 (18%) patients receiving monotherapy had serious adverse effects, two treatment-related deaths

NCT03563716

Active, not recruiting

Atezolizumab

Phase 3

NSCLC

–

–

–

–

NCT04294810 (SKYSCRAPER-01)

Recruiting

Atezolizumab, Carboplatin and Etoposide

Phase 3

ES-SCLC

–

5.4 months in the experimental group vs 5.6 months in the control group*

Both 13.6 months*

Grade 3/4 TRAEs occurred in 52.3% of the experimental group and 55.7% of the placebo group and Grade 5 TRAEs occurred in 0.4% of experimental group and 2.0% placebo group

NCT04256421 (SKYSCRAPER-02)

Active, not recruiting

Etigilimab (OMP-313M32)

Nivolumab

Phase 1

Advanced or metastatic cancer

No DLT detected. The maximum administered dose was 20 mg/kg. Besides, in the phase Ia study, seven patients (30.0%) had SD, and no PR was reported; in the phase Ib study, one patient had a partial response. One patient had prolonged SD of nearly eight months

56.0 days in phase 1a, 57.5 days in phase 1b

–

The most reported AEs were rash (43.5%), nausea (34.8%), and fatigue (30.4%) in phase Ia and decreased appetite (50.0%), nausea (50.0%), and rash (40%) in Phase Ib. Six patients experienced Grade ≥ 3 treatment-related AEs*

NCT03119428

Terminated