Table 2.
Summary of ongoing clinical trials of receptor inhibitors.
| Target | Drug | Number of Current Trials/ Phase |
Type of Tumor | Some Published Results of Clinical Trials | |
|---|---|---|---|---|---|
| Trial | Clinical Safety and Efficacy | ||||
| TIM-3 | Sabatolimab (MBG453) |
16 I, II, III |
Advanced or metastatic solid tumors Bone marrow diseases Glioblastoma Hematologic malignancies |
NCT02608268 Phase I-Ib/II |
Patients received sabatolimab (n = 133) or sabatolimab plus spartalizumab (n = 86). The MTD was not reached. No responses were seen with sabatolimab. Five patients receiving combination treatment had PR (6%; lasting 12–27 months) [51] |
| TSR-022 | 4 I, II |
Advanced or metastatic solid tumors Melanoma |
NCT02817633 Phase I |
In the group of 20 patients who received the TSR-022+TSR-042 combination, the ORR was 15% (3/20), and disease stabilization reached 40% (8/20) [52]. |
|
| LY3321367 | 1 I |
Solid tumors |
NCT03099109 Phase I |
No DLTs were observed in the monotherapy (n = 30) or combination (n = 28) therapy. LY3321367 TRAEs occurred in ≥2 patients. In the NSCLC 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% [53] |
|
| LY3415244, BsAb for PD-L1/TIM-3 |
1 I |
Advanced solid tumors |
NCT03752177 Phase Ia/Ib |
Two patients (16.7%) developed clinically significant anaphylactic infusion-related reactions. One patient with PD-1 refractory NSCLC had a near partial response (−29.6%) [54] |
|
| INCAGN02390 | 5 I |
Solid tumors Melanoma |
- | - | |
| BGB-A425 | 1 I |
Advanced or metastatic solid tumors | - | - | |
| BMS-986258 | 1 I |
Advanced cancer | - | - | |
| SHR-1702 | 2 I |
Hematologic malignancies Advanced solid tumors | - | - | |
| RO7121661, BsAb for PD-1/TIM-3 |
2 I, II |
Advanced or metastatic solid tumors Melanoma |
- | - | |
| LAG-3 | Eftilagimod alpha (IMP321) | 14 I, II |
Advanced or metastatic solid tumors Melanoma |
NCT00732082 Phase I |
None of the 6 patients received 0.5 mg IMP321 experienced TRAEs. Of the 5 patients who received IMP321 at the 2 mg dose level, 1 experienced rash, 1 reported hot flashes, and 2 had mild pain at the injection sites [85] |
|
NCT00349934 Phase I |
Thirty patients received IMP321 in three cohorts (doses: 0.25, 1.25 and 6.25 mg). Clinical benefit was observed for 90% of patients with only 3 progressors at 6 months. Additionally, t he ORR of 50% compared favorably to the 25% rate reported in the historical control group [86]. |
||||
| Favezelimab (MK-4280) |
10 I, II, III |
Advanced or metastatic solid tumors Hematologic malignancies Melanoma |
NCT03598608 Phase I/II |
Fifteen patients received MK-4280 with pembrolizumab, four of whom achieved a partial response [87] |
|
| Relatlimab (BMS-986016) |
31 I, II |
Advanced or metastatic solid tumors Hematologic malignancies Melanoma |
NCT01968109 Phase I/IIa |
Patients received relatlimab + nivolumab. In 61 efficacy-evaluable patients, ORR was 11.5% (1 complete, 6 partial (1 unconfirmed) responses); DCR was 49%. Median DOR was not reached (min [0.1þ], max [39.3þ]). ORR was 3.5-fold higher in patients with LAG-3 expression, 1% vs. <1%, regardless of PD-L1 expression. TRAEs occurred in 41% (gr 3/4, 4.4%; DC, 1.5%) [89] |
|
|
NCT03470922 Phase II |
The median PFS was 10.1 months (95% confidence interval [CI], 6.4 to 15.7) with relatlimab–nivolumab as compared with 4.6 months (95% CI, 3.4 to 5.6) with nivolumab (hazard ratio for progression or death, 0.75 [95% CI, 0.62 to 0.92]; p = 0.006 by the log-rank test). PFS at 12 months was 47.7% (95% CI, 41.8 to 53.2) with relatlimab–nivolumab as compared with 36.0% (95% CI, 30.5 to 41.6) with nivolumab. Grade 3 or 4 TRAEs occurred in 18.9% of patients in the relatlimab–nivolumab group and in 9.7% of patients in the nivolumab group [90]. | ||||
| TSR-033 | 2 I |
Advanced solid tumors | - | - | |
| REGN3767 | 5 I, II, III |
Advanced solid tumors | - | - | |
| Ieramilimab (LAG525) | 5 I, II |
Advanced solid tumors Hematologic malignancies Melanoma |
NCT02460224 Phase I/II |
Patients received fermilab (n = 134) or fermilab + spartalizumab (n = 121). Four patients experienced DLT in each treatment arm. No MTD was reached. TRAEs occurred in 75 (56%) and 84 (69%) patients in the single-agent and combination arms, respectively. Seven patients experienced SAEs in the single-agent (5%) and combination groups (5.8%). Antitumor activity was observed in the combination arm, with 3 (2%) CR and 10 (8%) PR. In the combination arm, 8 patients (6.6%) experienced SD for 6 months or longer versus 6 patients (4.5%) in the single-agent arm [93] |
|
| FS118, BsAb for LAG-3/PD-L1 |
1 I, II |
Advanced solid tumors Hematologic malignancies Melanoma |
- | - | |
| RO7247669, BsAb for LAG-3/PD-1 |
5 I, II |
Advanced or metastatic solid tumors Melanoma |
- | - | |
| TIGIT | Vibostolimab (MK-7684) |
15 I, II, III |
Advanced or metastatic solid tumors Melanoma Hematologic malignancies |
NCT02964013 Phase I |
Part A: 56% of patients receiving monotherapy and 62% receiving a combination of vibostolimab with pembrolizumab had TRAEs. Grade 3–4 TRAEs occurred in 9% and 17% of patients, respectively. No DLT was reported. The confirmed ORR was 0% for monotherapy and 7% for combination therapy. Part B: 39 patients had anti-PD-1/PD-L1-naive NSCLC, and all received combination therapy. TRAEs occurred in 85% of patients. The confirmed ORR was 26%, with responses observed in both PD-L1-positive and PD-L1-negative tumors. Sixty-seven had anti-PD-1/PD-L1-refractory NSCLC, and 56% receiving monotherapy and 70% receiving combination therapy had TRAEs. The confirmed ORR was 3% for monotherapy and 3% for combination therapy [131] |
| BMS-986207 | 4 I, II |
Advanced solid tumors Multiple myeloma |
- | - | |
| Etigilimab (OMP-313M32) |
2 I, II |
Advanced or metastatic solid tumors |
NCT03119428 Phase Ia/Ib |
Thirty-three patients were enrolled (Phase Ia, n = 23; Phase Ib, n = 10). There was no DLT. MTD was not determined. Six patients experienced grade ≥ 3 TRAEs. In Phase Ia, 7 patients (30.0%) had stable disease. In Phase Ib, 1 patient had a PR; 1 patient had prolonged SD of nearly 8 months. Median PFS was 56.0 days (Phase Ia) and 57.5 days (Phase Ib) [133] |
|
| Tiragolumab | 38 I, II, III |
Advanced or metastatic solid tumors Melanoma Hematologic malignancies |
NCT02864992 Phase II |
The RR by independent review was 46% (95% CI, 36 to 57), with a median DoR of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The RR was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed RR was 56% (95% CI, 45 to 66). TRAEs of grade ≥ 3 were reported in 28% [134] |
|
|
NCT03563716 Phase II |
Patients were randomly assigned to receive tiragolumab + atezolizumab (67 (50%)) or placebo + atezolizumab (68 (50%)). After a median follow-up of 5.9 months (4.6–7.6, in the intention-to-treat population, 21 patients (31.3% [95% CI 19.5–43.2]) in the tiragolumab + atezolizumab group versus 11 patients (16.2% [6.7–25.7]) in the placebo + atezolizumab group had an objective response (p = 0.031). Median PFS was 5.4 months (95% CI 4.2-not estimable) in the tiragolumab + atezolizumab group versus 3·6 months (2.7–4.4) in the placebo + atezolizumab group (stratified hazard ratio 0.57 [95% CI 0.37–0.90], p = 0.015). Fourteen (21%) patients receiving tiragolumab + atezolizumab and 12 (18%) patients receiving placebo + atezolizumab had SAEs [135] |
||||
| Domvanalimab (AB154) |
9 I, II, III |
Advanced or metastatic solid tumors Melanoma Glioblastoma |
- | - | |
| ASP8374 | 3 I |
Advanced solid tumors Glioblastoma |
- | - | |
| VISTA | CI-8993 | 1 I |
Solid tumors | - | - |
| CA-170, VISTA/PD-L1/2 antagonist | 2 I, II |
Advanced or metastatic solid tumors lymphomas |
NCT02812875 Phase I |
According to the RECIST, 33 out of 50 patients who received CA-170 showed SD. PR or CR was not achieved. Severe (grade 3 and 4) TRAEs were observed in 5 patients. No DLTs were observed [171]. | |
| JNJ-61610588 | 1 I |
Advanced or metastatic solid tumors | - | - | |
| BTLA | TAB004/JS004 | 7 I, II |
Recurrent/ refractory malignant lymphoma Advanced or metastatic solid tumors |
- | - |