Table 3.
Selected ongoing clinical trials targeting different TNFSF/TNFRSF members
| NCT ID | Drug of interest | Diagnosis | Target | Trial design | Setting | Rationale | No. of participants | Estimated completion year |
|---|---|---|---|---|---|---|---|---|
| NCT03298763 | MSCTRAIL | Non-small cell lung cancer | Mesenchymal stromal cells expressing TRAIL | Phase I/II multicenter, randomized double-blind placebo-controlled | Combination therapy (pemetrexed/cisplatin chemotherapy) | Delivering TRAIL-expressing cells to selectively induce apoptosis | 46 | 2025 |
| NCT04570631 | Eftozanermin alfa | Relapsed/refractory multiple myeloma | TRAIL receptor agonist | Phase I non-randomized trial | Combination with IV or subcutaneous (SC) bortezomib and oral dexamethasone tablet | Fusion protein based on TRAIL to selectively induce apoptosis | 40 | 2024 |
| NCT04950075 | INBRX-109 | Conventional chondrosarcoma | Death receptor 5 (DR5) antibody | Phase II randomized, blinded, placebo-controlled trial | Single-agent INBRX-109 | DR5 activation to induce cell death | 201 | 2024 |
| NCT04807972 | ABBV-927 | Pancreatic cancer | CD40 agonistic antibodies | Phase 1b/2, randomized, controlled, open-label study | ABBV-927 administered in combination with modified FOLFIRINOX (mFFX) with or without budigalimab | Promote immune responses using the CD40 axis | 40 | 2024 |
| NCT03502330 | APX005M | Melanoma, non-small cell lung cancer, and renal cell carcinoma | CD40 agonistic antibodies | A Phase I/Ib single-arm trial | APX005M in combination with nivolumab and cabiralizumab | Promote immune responses using the CD40 axis | 42 | 2027 |
| NCT03739931 | mRNA-2752 | Relapsed/refractory solid tumor malignancies or lymphoma | Lipid nanoparticle encapsulating mRNAs encoding human OX40L, IL-23, and IL-36γ | A Phase 1, open-label, multicenter, dose-escalation study | Intra-tumoral Injection alone and in combination with immune checkpoint blockade | OX40L, IL-23, and IL-36γ pro-inflammatory cytokines to promote immune responses | 264 | 2025 |
| NCT03092856 | PF-04518600 | Renal cell carcinoma | OX40 agonistic antibodies | Phase II randomized trial | Axitinib with or without anti-OX40 antibody | Promote immune responses using the OX40 axis | 62 | 2025 |
| NCT02830724 | Anti-hCD70 CAR transduced T cells | CD70-expressing cancers | Anti-CD70 CAR-T | Phase I/II non-randomized trial | Administering peripheral blood lymphocytes transduced with CD70-CAR-T cells | CD70-specific CAR-T to target CD-70-expressing cancer cells | 124 | 2028 |
| NCT04696731 | ALLO-316 | Renal cell carcinoma | Anti-CD70 CAR-T | Phase I single-arm trial | Lymphodepletion regimen of fludarabine, cyclophosphamide, and ALLO-647 followed by CD70 CAR-T therapy | CD70-specific CAR-T to target CD-70-expressing cancer cells | 120 | 2025 |
| NCT04903873 | EU101 | Advanced solid tumors | 4-1BB agonistic antibodies | Phase I/II single-arm trial | Single-agent EU101 | Promote immune responses using the 4-1BB axis | 110 | 2025 |
| NCT02845323 | Urelumab | Muscle-invasive urothelial carcinoma of the bladder | 4-1BB agonistic antibodies | Phase II randomized, blinded, controlled trial | Neoadjuvant nivolumab with or without urelumab (4-1BB agonistic antibodies) | Promote immune responses using the 4-1BB axis | 15 | 2024 |
| NCT05301764 | LVGN6051 | Soft tissue sarcoma | 4-1BB agonistic antibodies | Phase I/II single-arm trial | LVGN6051 combined with anlotinib | Promote immune responses using the 4-1BB axis | 65 | 2025 |
| NCT05117242 | Acasunlimab | Non-small cell lung cancer | 4-1BB agonistic antibodies | Phase II randomized, open-label, controlled trial | Acasunlimab with or without pembrolizumab | Promote immune responses using the 4-1BB axis | 160 | 2024 |
| NCT05192486 | GNC-038 | Diffuse large B-cell lymphoma | CD19xCD3 × 4-1BBxPD-L1 tetra-specific antibody | Phase Ib/II, open-label, multi-center study | Single-agent GNC-038 | Tetra-specific antibody to activate and enhance immune response and decrease immune system suppuration | 20 | 2024 |
| NCT04225039 | INCAGN01876 | Glioblastoma | GITR agonistic antibodies | Phase II non-randomized trial | Anti-GITR agonist INCAGN1876 and the PD-1 inhibitor INCMGA00012 in combination with stereotactic radiosurgery followed with/without surgery | Promote immune responses using the GITR axis | 39 | 2025 |
| NCT04021043 | BMS-986156 | Advanced solid tumors | GITR agonistic antibodies | Phase I/II non-randomized trial | Ipilimumab or nivolumab with BMS-986156 and hypofractionated stereotactic radiation therapy | Promote immune responses using the GITR axis | 68 | 2024 |
| NCT05891080 | JS004 | Non-small cell lung cancer | BTLA antagonist antibodies | Phase II randomized trial | Neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy | Promote immune responses by inhibiting the BTLA axis | 124 | 2030 |
| NCT05427396 | JS004 | Advanced solid tumors | BTLA antagonist antibodies | Phase I single-arm trial | Recombinant humanized anti-btla monoclonal antibody (JS004) injection combined with oripalimab | Promote immune responses by inhibiting the BTLA axis | 198 | 2025 |
| NCT05664971 | JS004 | Non-small cell lung cancer | BTLA antagonist antibodies | Phase Ib/II single-arm trial | Recombinant humanized anti-BTLA monoclonal antibody (JS004) injection combined with toripalimab and with standard chemotherapy | Promote immune responses by inhibiting the BTLA axis | 240 | 2024 |
| NCT05069051 | Belimumab | Chronic lymphocytic leukemia | BAFF antagonist antibodies | Phase II randomized trial | Rituximab/venetoclax with or without belimumab | Promote sensitivity to rituximab/venetoclax by inhibiting the BTLA axis | 120 | 2027 |
| NCT05546723 | LMY-920 | Relapsed/refractory multiple myeloma | BAFF-based CAR-T | Phase I single-arm trial | Single-agent LMY-920 | BAFF-specific CAR-T to target BAFF receptors-expressing cancer cells | 30 | 2024 |
| NCT04879043 | HDP-101 | Relapsed/refractory multiple myeloma | BCMA antibody–drug conjugates | Phase I/II | Single-agent HDP-101 | Antibody–drug conjugates targeting BCMA-expressing cells with amanitin (RNA polymerase II inhibitor) as the payload | 78 | 2025 |