Table 2.
Clinical trials on VISTA, CD39, CD73, and CD38
| Target | Drug | Combination agent | Phase | Tumor type | Clinical efficacy | PFS | OS | Safety | Clinical trial | Status |
|---|---|---|---|---|---|---|---|---|---|---|
| VISTA | JNJ-61610588 | – | Phase1 | Advanced cancer | – | – | – | – | NCT02671955 | Terminated |
| CI-8993 | – | Phase1 | Solid tumor | – | – | – | – | NCT04475523 | Recruiting | |
| CA-170 | – | Phase 1 | Advanced solid tumors or lymphomas | Pharmacokinetics (PK) exposure with a t1/2 of 3.4 h for CA-170 | – | – | – | NCT02812875 | Completed | |
| – | Phase 2 | Advanced solid tumors or lymphomas | ORR of 30% in Classical Hodgkin lymphoma, CBR of > 85% at a daily dose of 400 mg and PFS of 19.6 weeks in stage 4 non-squamous NSCLC | 19.6 weeks | – | – | – | – | ||
| CD39 | TTX-030 | Pembrolizumab Docetaxel Gemcitabine nab-paclitaxel | Phase 1 | Solid tumor lymphoma | – | – | – | – | NCT03884556 | Active, not recruiting |
| Budigalimab Docetaxel mFOLFOX6 Gemcitabine nab-paclitaxel Pembrolizumab | Phase 1 | Solid tumor, adult | – | – | – | – | NCT04306900 | Active, not recruiting | ||
| SRF617 | Gemcitabine Albumin-Bound Paclitaxel Pembrolizumab | Phase 1 | Advanced solid tumor | – | – | – | – | NCT04336098 | Recruiting | |
| CD73 | HLX23 | – | Phase 1 | Advanced solid tumor | – | – | – | – | NCT04797468 | Not yet recruiting |
| LY3475070 | Pembrolizumab | Phase 1 | Advanced cancer | – | – | – | – | NCT04148937 | Active, not recruiting | |
| AK119 | AK104 | Phase 1 | Advanced or metastatic solid tumors | – | – | – | – | NCT04572152 | Recruiting | |
| CPI006 | Ciforadenant Pembrolizumab | Phase 1 | Advanced solid tumors | 1 patient (monotherapy) with metastatic CRPC: substantial reduction in the size of a target lesion after only 5 cycles, sustained at the time of cutoff | – | – | No DLTs reported* | NCT03454451 | Recruiting | |
| Sym024 | Sym021 | Phase 1 | Metastatic cancer solid tumor | – | – | – | – | NCT04672434 | Recruiting | |
| NZV930 | KAZ954 PDR001 NIR178 | Early Phase 1 | Solid tumors | – | – | – | – | NCT04237649 | Recruiting | |
| PDR001 NIR178 | Phase 1 | NSCLC TNBC PDAC MSS colorectal cancer ovarian cancer RCC mCRPC | – | – | – | – | NCT03549000 | Recruiting | ||
| MEDI9447 (Oleclumab) | Osimertinib AZD4635 | Phase 1 Phase 2 | Carcinoma, NSCLC | – | – | – | – | NCT03381274 | Active, not recruiting | |
| Durvalumab | Phase 1 | Muscle-invasive bladder cancer | – | – | – | – | NCT03773666 | Active, not recruiting | ||
| Paclitaxel Carboplatin MEDI4736 | Phase 1 Phase 2 | TNBC | – | – | – | – | NCT03616886 | Active, not recruiting | ||
| Durvalumab Tremelimumab MEDI 0562 | Phase 2 | Ovarian cancer | – | – | – | – | NCT03267589 | Completed | ||
| AZD4635 Durvalumab | Phase 2 | Prostate cancer mCRPC | Experimental group (n = 21): ORR 0.0%; positive control group (n = 20): ORR 5.0%* | rPFS 11.1 months for experimental group against 8.8 months for positive control group | Experimental group: NA; Positive control group: 10.72 months | Serious adverse events were 8/30 for experimental group, and 6/29 for control group | NCT04089553 | Active, not recruiting | ||
| Durvalumab | Phase 2 | Luminal B | – | – | – | – | NCT03875573 | Recruiting | ||
| Durvalumab Monalizumab | Phase 2 | Stage III NSCLC | – | – | – | – | NCT03822351 | Active, not recruiting | ||
| CD38 | CID-103 | – | Phase 1 | Multiple myeloma | – | – | – | – | NCT04758767 | Recruiting |
| Daratumumab | – | Phase 2 | Multiple myeloma | – | – | – | – | NCT04656951 | Recruiting | |
| – | Phase 1 Phase 2 | GBM | – | – | – | – | NCT04922723 | Not yet recruiting | ||
| – | Phase 2 | Multiple myeloma in relapse | – | – | – | – | NCT03697629 | Completed | ||
| – | Phase 2 | Plasma cell myeloma | – | – | – | No report | NCT02944565 | Completed | ||
| Phase 2 | Relapsed or refractory natural killer/T cell lymphoma | ORR 25.0%, CR 3.1%* | 53.0 days | 141.0 days | Serious adverse events: 17/32 | NCT02927925 | Completed | |||
| – | Phase 2 | Myeloma multiple | – | – | – | – | NCT03992170 | Recruiting | ||
| – | Phase 2 | Monoclonal gammopathy smoldering multiple myeloma | – | – | – | – | NCT03236428 | Active, not recruiting | ||
| – | Phase 4 | Multiple myeloma | – | – | – | – | NCT03768960 | Active, not recruiting | ||
| – | Phase 2 | Refractory T cell lymphoma relapsed T cell lymphoma | – | – | – | – | NCT04251065 | Active, not recruiting | ||
| Nivolumab Cyclophosphamide | Phase 2 | Myeloma | – | – | – | – | NCT03184194 | Active, not recruiting | ||
| – | Phase 2 | Multiple myeloma | – | – | – | – | NCT04230031 | Withdraw | ||
| Thalidomide and Dexamethasone | Phase 2 | Relapse and/or refractory myeloma | – | – | – | NCT03143036 | Unknown | |||
| Velcade, melphalan, and prednisone | Phase 3 | Multiple myeloma | The Kaplan–Meier estimate of the 36-month rate of OS was 78.0% (95% CI 73.2–82.0) in the D-VMP group and 67.9% (62.6–72.6) in the VMP group. PFS remained prominently improved for the D-VMP group (HR 0·42 [0·34–0·51]; p < 0·0001)* | – | – | Respiratory infections (54 of 278 patients had upper respiratory tract infections; 42 had bronchitis, and 34 had viral upper respiratory tract infections), cough (34), and diarrhea (28) | NCT02195479 (ALCYONE) | Active, not recruiting | ||
| Lenalidomide and Dexamethasone | Phase 3 | Multiple myeloma | mPFS was not reached (95% CI 54.8–not reached) in the patients with Rd compared with 34.4 months (29.6–39.2) in the control group* | NA;34.4 months* | NA | Serious adverse events occurred in 281 (77%) patients with DRd and 257 (70%) patients with Rd. Thirteen (4%) patients with DRd and ten (3%) patients with Rd underwent TRDs | NCT02252172 (MAIA) | Active, not recruiting | ||
| Bortezomib, Thalidomide, and Dexamethasone | Phase 3 | Multiple myeloma | 157 of 543 patients in the D-VTd group and 110 of 542 patients in the VTd group had achieved a stringent CR; CR was 211 vs 141, and 346 of 543 versus 236 of 542 achieved minimal residual disease negativity* | – | – | 46 deaths in the study were observed, and the most common grade 3 or 4 adverse events were neutropenia, lymphopenia, and stomatitis | NCT02541383 (VELCADE) | Active, not recruiting | ||
| MOR03087 (MOR202) | Dexamethasone Pomalidomide Lenalidomide | Phase 1 Phase 2 | Multiple myeloma | ORR 0.0% for MOR03087 Biweekly Dose Escalation and MOR03087 Weekly Dose Escalation, 27.8% for MOR03087 Plus Dexamethasone, 47.6% for MOR03087 Plus Pomalidomide + Dexamethasone, 64.7% for MOR03087 Plus Lenalidomide + Dexamethasone | In the given order, 1.1, 2.1, 8.4, 15.9, 26.7(months) | – | In the given order, serious adverse events: 13/31, 4/4, 7/18, 20/21, 14/17 | NCT01421186 | Completed | |
| Isatuximab | – | Phase 2 | Relapsed multiple myeloma refractory multiple myeloma | – | – | – | – | NCT04802031 | Withdraw | |
| Lenalidomide, Bortezomib, and Dexamethasone | Phase 3 | Transplant-eligible NDMM | Minimal residual disease (MRD) negative rate after induction therapy was 35.6% in the RVd group and 50.1% in the isatuximab–RVD group. The CR rate after induction therapy was 24.2% in the isatuximab–RVD group and 21.6% in the RVd group | – | – | At least one AE of grade 3 or higher occurred in 63.6% of patients in the isatuximab–RVD group and 61.3% in the RVd group, respectively. The incidence of serious AEs was 34.8% and 36.3% | GMMG-HD7 | – | ||
| Carfilzomib and Dexamethasone | Phase 3 | Relapsed multiple myeloma | mPFS was not reached in the isatuximab group compared with 19.15 months in the control group, with an HR of 0.53* | – | – | TEAEs of grade 3 or worse occurred in 136 of 177 patients in the isatuximab group versus 82 of 122 in the control group, serious TEAEs occurred in 105 versus 70 patients, and deaths were reported in six versus four patients | NCT03275285 | Active, not recruiting | ||
| Pomalidomide and Dexamethasone | Phase 3 | Relapsed and refractory multiple myeloma | mPFS was 11.5 months (95% CI 8.9–13.9) in the isatuximab group, compared with 65 months (4.5–8.3) in the control group | 11.5 months; 65 months* | – | Infusion reactions (56), upper respiratory tract infections (69), and diarrhea (68). Serious adverse events were reported in 12 patients (8%) in the isatuximab group and 14 (9%) in the control group | NCT02990338 | Active, not recruiting | ||
| Dexamethasone | Phase 2 | Relapsed multiple myeloma | – | – | – | – | NCT04965155 | Active, not recruiting | ||
| – | Phase 2 | Multiple myeloma | – | – | – | – | NCT04786028 | Recruiting | ||
| CellProtect | Phase 2 | Multiple myeloma | – | – | – | – | NCT04558931 | Recruiting | ||
| – | Phase 2 | Smoldering plasma cell myeloma | – | – | – | – | NCT02960555 | Recruiting | ||
| Bortezomib Dexamethasone | Phase 1 | Multiple myeloma | – | – | – | – | NCT04912427 | Recruiting | ||
| – | Phase 1 | Plasma cell myeloma | MR 3.1%, SD 53.1% | 1.6 | 10.7 | 16 (50.0%) patients had Grade ≥ 3 TEAE* | NCT02514668 | Completed | ||
| – | Phase 1 Phase 2 | Multiple myeloma | ORR 36.4%*, CBR 54.5% | 4.7 | – | No DLTs reported*. TEAEs of grade ≥ 3 included pneumonia in two patients, and intervertebral discitis, lung infection, disseminated intravascular coagulation, seizure, thrombotic cerebral infarction, ileus, and synovial cyst in one patient each | NCT02812706 | Active, not recruiting | ||
| Cemiplimab | Phase 2 | Natural killer/T cell lymphoma relapsed natural killer/T cell lymphoma refractory natural killer/T cell lymphoma | – | – | – | – | NCT04763616 | Recruiting | ||
| Carfilzomib Pomalidomide | Phase 2 | Recurrent plasma cell myeloma refractory plasma cell myeloma | – | – | – | – | NCT04850599 | Recruiting | ||
| – | Phase 1 | Multiple myeloma | – | – | – | – | NCT03733717 | Active, not recruiting | ||
| ISB 1342 | – | Phase 1 | Relapsed/refractory multiple myeloma | – | – | – | – | NCT03309111 | Recruiting | |
| GEN3014 | – | Phase 1 Phase 2 | Multiple myeloma | – | – | – | – | NCT04824794 | Recruiting |
*Primary endpoint; NSCLC, non-small -cell lung cancer; TNBC, triple-negative breast cancer; MSS, microsatellite stable; PDAC, pancreatic ductal adenocarcinoma; RCC, renal cell carcinoma; mCRPC, metastatic castration-resistant prostate cancer; GBM, glioblastoma