From:  Bispecific antibodies in the treatment of epithelial ovarian, endometrial, and cervical cancer: an overview of current applications, challenges, and emerging opportunities

 Summary of main clinical trials investigating bsAbs in cervical and ECs.

Drug nameTargetsSettingPhasenResultsTEAEs/TRAEs/irAEs G ≥ 3* (in at least 5% of pts) and any grade CRS/IRR/ICANS**
(%)
TAA mechanism
Zanidatamab (ZW25) [54]HER2 (ECD2) × HER2 (ECD4)R/M EC/carcinosarcoma
≤ 2 lines		216ORR: 6.2%
mPFS: 1.7 mths (90% CI: 1.6–4.1 mths)
OS: 14.5 mths (90% CI: 11.2–not estimable)

TRAEs G ≥ 3

  • no events ≥ 5%

Any grade

  • IRR 18.8%

  • CRS/ICANS NR

ICI mechanism
Cadonilimab (AK104)/placebo + cht +/– bev COMPASSION-16 [109, 112]PD-1 × CTLA-4R/M CC
1 line		3445 (all pts)
222 (cadonilimab group)
223 (placebo group)		ORR: 79% vs. 68%
mPFS: 13.3 vs. 8.2 mths (HR 0.62; 95% CI: 0.49–0.79, p < 0.0001)
mOS: NA vs. 22.8 mths (HR 0.64; 95% CI: 0.48–0.86, p = 0.0011)

TRAEs G ≥ 3

  • cadonilimab vs. placebo

    • neutropenia 41% vs. 46%

    • anemia 15.9% vs. 24.2%

    • platelet count decreased 14% vs. 12%

    • diarrhea 2% vs. 1%

    • hypokalemia 5.8% vs. 4.1%

    • hypertriglyceridemia 6.2% vs. 4.1%

    • hypertension 6.6% vs. 9.6%

irAEs G ≥ 3

  • cadonilimab vs. placebo

    • no events ≥ 5%

Any grade

  • IRR 11.9% vs. 2.3%

  • CRS/ICANS NR

Ivonescimab (AK112/SMT112) [95]PD-1 × VEGFR EC151 (all pts)
3 (EC)		ORR: 4.26%

TRAEs G ≥ 3

  • hypertension 13.7%

  • ALT increased 5.2%

irAEs G ≥ 3

  • no events ≥ 5%

Any grade

  • IRR 7.8%

  • CRS/ICANS NR

Tebotelimab (MGD013) +/– margetuximab [94]PD-1 × LAG-3R/M CC
1 line		1277 (all pts)
Monotherapy:
17 (EC)
Combination:
1 (EC)		ORR: 0

Monotherapy

  • TRAEs G ≥ 3

    • no events ≥ 5%

  • irAEs G ≥ 3

    • no events ≥ 5%

  • any grade

    • IRR 7.4%

    • CRS/ICANS NR

Combination

  • TRAE G ≥ 3

    • AST increased 5%

  • irAEs G ≥ 3

    • no events ≥ 5%

  • any grade

    • IRR 7.1%

    • CRS/ICANS NR

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The Table provides a comprehensive overview of the main clinical trials evaluating bispecific antibodies (bsAbs) in cervical and ECs. Only studies with available clinical data in these tumor types are reported, with a focus on target specificity, study phase, treatment combinations, and preliminary efficacy or safety outcomes, when available. *: Some trials reported treatment-related adverse events (TRAEs), other treatment-emergent adverse events (TEAEs), and immune-related adverse events (irAEs). Only grades ≥ 3 observed in more than 5% of patients are included in this Table; **: adverse events of special interest (AESIs), including cytokine release syndrome (CRS), infusion-related reaction (IRR), and immune effector cell-associated neurotoxicity syndrome (ICANS), are listed in the Table regardless of grade and even if occurring in less than 5% of patients. G: grade; TAA: tumor-associated antigen; HER2: human epidermal growth factor receptor 2; ECD2: extracellular domain 2; ECs: endometrial cancers; ORR: objective response rate; mPFS: median progression-free survival; mths: months; CI: confidence interval; OS: overall survival; mOS: median OS; NR: not reported; ICI: immune checkpoint inhibitor; cht: chemotherapy; bev: bevacizumab; PD-1: programmed cell death protein 1; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; R/M: recurrent/metastatic; CC: cervical cancer; pts: patients; HR: hazard ratio; NA: not available; VEGF: vascular endothelial growth factor; R: recurrent; ALT: alanine aminotransferase; LAG-3: lymphocyte activation gene 3; AST: aspartate aminotransferase.