Table 2 The results of representative clinical trials of bispecific/bifunctional antibodies targeting PD-1/PD-L1 signaling
From: The enhanced antitumor activity of bispecific antibody 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% |