Table 4.
Clinical trials on IDO-1 and CD27
| Target | Drug | Combination agent | Phase | Tumor type | Clinical efficacy | PFS | OS | Safety | Clinical trial | Status |
|---|---|---|---|---|---|---|---|---|---|---|
| IDO-1 | Epacadostat (INCB24360) | – | Phase 1 | Rectal Cancer | – | – | – | – | NCT03516708 | Recruiting |
| MEDI4736 | Phase 1 Phase 2 | Solid Tumors Head and Neck Cancer Lung Cancer UC | In the study, attendants were divided into 6 groups, ORR was 16.7%, 0.0%, 25.0%, 0.0%, 12.5%, 22.2% for each group; ORR 12.2% for attendants received Epacadostat (100 mg) + Durvalumab (10 mg/kg), and that was 12.9% for participants received Epacadostat (300 mg) + Durvalumab (10 mg/kg)* | 2.4, 12.0, 1.9, 1.7, 4.12.5 1.9 and 2.1 | – | Serious adverse events were 2/6, 0/3, 2/4, 0/4, 4/8, 3/9 for each group. Serious adverse events were 20/49, 54/93 for each group | NCT02318277 (ECHO-203) | Completed | ||
| Pembrolizumab | Phase 3 | UC | Experimental group (n = 44): ORR 31.8%; positive control group (n = 49): ORR 24.5%* | – | – | Serious adverse events were 23/43 against 23/49 | NCT03361865 (KEYNOTE-672/ECHO-307) | Completed | ||
| Pembrolizumab | Phase 1 Phase 2 | Advanced melanoma | – | – | – | – | NCT02178722 (ECHO-202/KEYNOTE-037) | Completed | ||
| Fludarabine Cyclophosphamide | Phase 1 | Ovarian Cancer Fallopian Tube Carcinoma Primary Peritoneal Carcinoma | – | – | – | – | NCT02118285 | Completed | ||
| Pembrolizumab | Phase 2 | Lung Cancer | Experimental group (n = 77): ORR 32.5%; control group (n = 77): ORR 39.0%* | Experimental group: 6.7; control group: 6.2 | NA | Serious adverse events were 23/75 for experimental group, and 29/77 for control group | NCT03322540 (KEYNOTE-654–05/ECHO-305–05) | Completed | ||
| Pembrolizumab | Phase 2 | Thymic Carcinoma Thymus Neoplasms Thymus Cancer | 1/40 attendant had a complete response, 8/40 participants had partial response, 21/40 participants received stable disease, 10/40 participants suffered progression* | 4.2 | 24.9 | 2/40 patients suffered myocarditis, one case for hyperglycemia, hepatitis, bullous pemphigoid, and polymyositis each | NCT02364076 | Unknown | ||
| Pembrolizumab Platinum-based chemotherapy | Phase 2 | Lung Cancer | Experimental group (n = 91): ORR 26.4%; control group (n = 87): ORR 44.8%* | Experimental group: 8.0; control group: 8.2 | NA | Serious adverse events were 47/90 against 41/86 | NCT03322566 (KEYNOTE-715–06/ECHO-306–06) | Completed | ||
| Pembrolizumab | Phase 3 | UC | Experimental group (n = 42): ORR 21.4%; control group (n = 42): ORR 9.5%* | – | – | Serious adverse events were 22/42 for experimental group, and 16/41 for control group | NCT03374488 (KEYNOTE-698/ECHO-303) | Completed | ||
| – | Phase 1 | Solid Tumors and Hematologic Malignancy | – | – | – | – | NCT01195311 | Completed | ||
| Pembrolizumab | Phase 2 | Gastrointestinal Stromal Tumors | – | – | – | – | NCT03291054 | Completed | ||
| Pembrolizumab Cetuximab Cisplatin Carboplatin 5-Fluorouracil | Phase 3 | Head and Neck Cancer | Experimental group (n = 35): ORR 31.4%; negative control group (n = 19): ORR 21.1%; positive control group (n = 35): ORR 34.3%* | – | Serious adverse events were 12/34 for experimental group, 8/19 for negative control group, and 12/34 for positive control group | NCT03358472 (KEYNOTE-669/ECHO-304) | Active, not recruiting | |||
| Low dose cyclophosphamide | Phase 1 Phase 2 | Breast Cancer Female Breast Neoplasm Female | – | – | – | – | NCT03328026 | Recruiting | ||
| BMS-986205 | Nivolumab | Phase 2 | Endometrial Adenocarcinoma and Endometrial Carcinosarcoma | – | – | – | – | NCT04106414 | Active, not recruiting | |
| Nivolumab | Phase 3 | Melanoma Skin Cancer | – | – | – | Serious adverse events were 4/10 for experimental group against 4/10 for control group* | NCT03329846 | Completed | ||
| Nivolumab | Phase 1 Phase 2 | Advanced Cancer | – | – | – | Two cases for malignant neoplasm progression, one case for tuberculosis, acute kidney injury, pneumonitis each | NCT03792750 | Completed | ||
| – | Phase 1 | Cancer | – | – | – | – | NCT03247283 | Completed | ||
| Nivolumab Gemcitabine Cisplatin Placebo | Phase 3 | Bladder Cancer Muscle-Invasive Bladder Cancer | – | – | – | – | NCT03661320 | Recruiting | ||
| Itraconazole Rifampin | Phase 1 | Malignancies Multiple | – | – | – | – | NCT03346837 | Completed | ||
| Nivolumab | Phase 1 | Advanced Cancer | – | – | – | – | NCT03192943 | Completed | ||
| Nivolumab Ipilimumab | Phase 1 Phase 2 | Advanced Cancer Melanoma NSCLC | – | – | – | – | NCT02658890 | Recruiting | ||
| CD27 | Varlilumab (CDX-1127) | – | Phase 1 Phase 2 | B Cell Lymphoma | – | – | – | – | NCT03307746 | Active, not recruiting |
| nivolumab | Phase 1 Phase 2 | HNSCC Ovarian Carcinoma-Enrollment Completed CRC-Enrollment Completed RCC (Phase ll Only) GBM (Phase ll Only)-Enrollment Completed | – | – | – | – | NCT02335918 | Completed | ||
| – | Phase 1 | Selected refractory or relapsed hematologic malignancies or solid tumors | A patient with mRCC underwent a partial response (78% shrinkage) and had a durable response with PFS > 2.3 years without additional treatment. Eight patients underwent SD > 3 months, including a patient with metastatic RCC with PFS of > 3.9 years | – | – | Only one case with grade 3 transient asymptomatic hyponatremia was reported. Other adverse events were limited to grade 1 or 2 in severity* | NCT01460134 | Completed | ||
| Atezolizumab Cobimetinib | Phase 2 | Unresectable Liver and Intrahepatic Bile Duct Carcinoma | – | – | – | – | NCT04941287 | Recruiting | ||
| ONT-10 | Phase 1 | Advanced Breast Carcinoma Advanced Ovarian Carcinoma | – | – | – | – | NCT02270372 | Completed | ||
| Rituximab | Phase 2 | Relapsed or refractory B cell malignancies | – | – | – | Three Grade 3 treatment-related events in the study, including hyponatremia, decreased appetite, and decreased lymphocyte count | ISRCTN15025004 | Ongoing | ||
| Atezolizumab | Phase 1 | Refractory NSCLC Stage IV Lung Cancer AJCC v8 | – | – | – | – | NCT04081688 | Recruiting | ||
| IMA950 poly-ICLC | Phase 1 | Glioma Malignant Glioma Astrocytoma, Grade II Oligodendroglioma Glioma, Astrocytic Oligoastrocytoma, Mixed | – | – | – | – | NCT02924038 | Active, not recruiting | ||
| MHP Montanide ISA-51 poly-ICLC | Phase 1 Phase 2 | Melanoma | – | – | – | – | NCT03617328 | 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