Table 5.
Clinical trials on TIM-3, BTLA, CD47, B7-H3, B7-H4, CD70, and TIGIT
| Target | Drug | Combination agent | Phase | Tumor type | Clinical efficacy | PFS | OS | Safety | Clinical trial | Status |
|---|---|---|---|---|---|---|---|---|---|---|
| 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 |
*Primary endpoint; NSCLC, non-small-cell lung cancer; TNBC, triple-negative breast cancer; MSS, microsatellite stable; HNSCC, head and neck squamous cell carcinoma; ESCC, esophageal squamous cell carcinoma; SCLC, small-cell lung cancer; MDS, myelodysplastic syndrome; AML, acute myeloid leukemia; CRC, colorectal cancer; RCC, renal cell carcinoma; GBM, glioblastoma; UC, urothelial cancer