Table 2.
The results of representative clinical trials of bispecific/bifunctional antibodies targeting PD-1/PD-L1 signaling
| Targets | Agents | Clinical trials | Cancer types | Results |
|---|---|---|---|---|
| TGFβ × PD-L1 | M7824 | NCT02517398 | NSCLC | ORR of PD-L1-positive at 1200 mg dose: 36.0%; ORR of PD-L1-high at 1200 mg dose: 85.7% |
| SHR-1701 | NCT05179239 | Cervical cancer | ORR: 15.6%; DCR: 50.0% | |
| NCT03710265 | Solid tumors | Clinical-expansion part of gastric cancer cohort: ORR of 20.0% and 12-month OS rate of 54.5% | ||
| TQB2858 | CTR20213001 | Osteosarcoma and ASPS | PFS: 8.34 months; OS: 9.63 months | |
| PM8001 | ChiCTR2000033828 | Advanced solid tumors | RP2D: 20 mg/kg Q2W; ORR: 10.4%; DCR: 53.7% | |
| TST005 | NCT04958434 | Advanced solid tumors | DCR: 63.6% (SD, none achieving CR or PR) | |
| CD47 × PD-L1 | PF-07257876 | NCT04881045 | Advanced solid tumors | DoR: 16 weeks for SCCHN; ORR: 5.6% |
| VEGF × PD-1 | AK112 (Ivonescimab) | NCT04736823 | NSCLC | SCC: ORR: 75%, median DOR: 15.4 months, DCR: 95%; non-SCC: ORR: 55%, DCR: 100% |
| NCT04900363 | NSCLC | For all patients: ORR: 39.8%, DCR: 86.1%; ORR (TPS < 1%): 14.7%, ORR (TPS ≥ 1%): 51.4%, ORR (TPS ≥ 50%): 57.1%. ORR of dose at 30 mg/kg Q3W for PD-L1 positive: 75.0% | ||
| VEGF × PD-L1 | HB0025 | NCT04678908 | Advanced solid tumors | ORR of dosed at ≥ 3 mg/kg Q2W: 9.1%; DCR of dosed at ≥ 3 mg/kg Q2W: 50% |
| PM8002 | ChiCTR2200060400 | TNBC | ORR: 69.2%; DCR: 92.3% | |
| ChiCTR2000040552 | Advanced solid tumors | ORR: 15.2%; DCR: 75.4%. ORR (cervical cancer):28%; ORR (renal cell carcinoma): 26.9%; ORR (platinum-resistant ovarian cancer): 15.4%; ORR (NSCLC with EGFR mutations): 18.5% | ||
| ChiCTR2200059911 | SCLC | ORR: 72.7%; DCR: 81.8% (18/22); Median PFS: 5.5 months | ||
| 4-1BB × PD-L1 | PM1003 | ChiCTR2100052887 | Advanced solid tumors | ORR: 5.6%; DCR: 44.4% |
| GEN1046 | NCT03917381 | Advanced solid tumors | DCR: 65.6% | |
| LAG-3 × PD-L1 | FS118 | NCT03440437 | Advanced solid tumors | RP2D: 10 mg/kg weekly; DCR: 46.5% |
| LAG-3 × PD-1 | Tebotelimab (MGD013) | NCT04178460 | Gastric cancer | RP2D: 600 mg Q2W; ORR: 5.3%; DCR: 52.6%; Median PFS: 2.7 months; Median OS: 6.5 months |
| NCT03219268 | Advanced solid tumors | RP2D: 600 mg Q3W; ORR: 19% | ||
| EMB-02 | NCT04618393 | Advanced solid tumors | DCR: 44.7%; CBR-24 (CR + PR + durable SD [≥ 24weeks]): 19% | |
| RO7247669 | NCT04140500 | Advanced solid tumors | ORR: 17.1%; DCR: 51.4% | |
| CTLA-4 × PD-1 | QL1706 | NCT05329025 | NSCLC | Wild-type EGFR: ORR: 45%; median PFS: 6.8 months; Mutated EGFR: ORR: 54.8%; median PFS: 8.5 months |
| NCT05603039 | Advanced HCC | ORR: 38.3%; DCR: 74.5%; Median PFS: 6.7 months | ||
| NCT04296994 and NCT05171790 | Advanced solid tumors | RP2D: 5 mg/kg; ORR: 16.9%, 14.0% (NSCLC), 24.5% (NPC), 27.3% (cervical cancer), 7.4% (colorectal cancer), 23.1% (SCLC); DoR: 11.7 months | ||
| NCT05179317 | Cervical cancer | ORR: 81%; DCR: 98.3%; Median PFS: 14.3 months | ||
| NCT05309629 | ES-SCLC | ORR: 89.7%; DCR: 97.4% | ||
| MGD019 (Lorigerlimab) | NCT03761017 | Advanced solid tumors | ORR: 16%; DCR: 36% | |
| AK104 (Cadonilimab) | NCT05522894 | ESCC | ORR1: 86.7%; DCR: 100.0%; ORR (PD-L1 CPS ≥ 10): 83.3%; ORR (PD-L1 CPS < 10): 88.9% | |
| NCT03852251 | Advanced solid tumors | ORR (Cervical cancer): 32.3%; ORR (ESCC): 18.2%; ORR (HCC): 19.6% | ||
| NCT04646330 | NSCLC | ORR of dosed at 15 mg/kg Q3W: 51%; ORR of dosed at 10 mg/kg Q3W: 60% | ||
| NCT04444167 | HCC |
Dosed at 6 mg/kg Q2W: ORR: 35.5%; Median DoR: 13.6 months; Median PFS: 8.6; Median OS was 27.1 months; Dosed at 15 mg/kg Q3W: ORR: 35.7%; DCR: 13.67 months; Median PFS: 9.8 months |
||
| CTLA-4 × PD-L1 | KN046 | NCT03872791 | TNBC | ORR: 44.0%; PFS: 7.33 months; OS: 30.92 months; PD-L1 + PFS: 8.61 months; 2-year OS rate: 62.5%; PD-L1-: PFS: 4.73 months; 2-year OS rate: 57.1% |
| NCT03838848 | NSCLC |
Dosed at 3 mg/kg Q2W: ORR: 13.3%; PFS: 3.68 months; OS: 19.7 months Dosed at 5 mg/kg Q2WW: ORR: 14.7%; PFS: 3.68 months; OS: 13.04 months |
||
| NCT04469725 | Thymic carcinoma | ORR: 16.3%; DoR: 10.1 months; PFS: 5.6 months; 18-months OS rate: 74.1% | ||
| NCT04521179 | HER2 + gastric or GEJ cancer | ORR: 77.8%; DCR: 92.6% | ||
| NCT04324307 | PDAC | ORR: 11.1%; DCR: 44.4%; PFS: 2.1 months; OS: 7.5 months | ||
| NCT03925870 | ESCC | ORR: 58.3%; DCR: 91.6% | ||
| TIM-3 × PD-L1 | LY3415244 | NCT03752177 | Advanced solid tumors | 1/12 reaching PR |
| TIM-3 × PD-1 | AZD7789 | NCT04931654 | Advanced NSCLC | 7/19 reaching SD |
| PD-1 × PD-L1 | IBI318 | NCT03875157 | Advanced solid tumors | 3/9 of dose ≥ 10mg Q2W reaching PR |
| TIGIT × PD-1 | AZD2936 (Rilvegostomig) | NCT04995523 | NSCLC | ORR: 3.9%; DCR: 43.4% |
Annotations: ORR Objective response rate, DCR Disease control rate, OS Overall survival, NSCLC Non-small cell lung cancer, ASPS Alveolar soft part sarcoma, PFS Progression free survival, CR Complete response, PR Partial response, SCCHN Squamous cell carcinoma of the head and neck, DoR Duration of response, TPS Tumor proportion score, TNBC Triple-negative breast cancer, RP2D Recommended phase 2 dose, SD Stable disease, HCC Hepatocellular carcinoma, NPC Nasopharyngeal carcinoma, SCLC Small cell lung cancer, ESCC Esophageal squamous cell carcinoma, GEJ Gastroesophageal junction, PDAC Pancreatic ductal adenocarcinoma