Table 1.
ADCs in clinical development for gynecologic malignancies
| ADC | Target | Payload and DAR | Company | Status | Key trials |
| Pan tumor | |||||
| Trastruzumab deruxtecan | HER2 | Deruxtecan (Ti) 8 |
AstraZeneca | FDA approved – HER2 3+ tumors | Phase II: DESTINY-PanTumor02 [40▪▪] |
| IBI354 | HER2 | Camptothecin derivative (Ti) 8 |
Innovent Biologics | Phase I/II ongoing | Phase I/II: NCT05636215 |
| Ovarian | |||||
| Mirvetuximab soravtansine | FRα | DM4 (MTi) 4 |
AbbVie/ ImmunoGen | FDA approved- PROC, ongoing trials for PSOC | Phase III: MIRASOL [12▪▪], FORWARD I [13▪▪] Ongoing: FORDWARD II, PICCOLO GLORIOSA, IMGN853-0420 |
| Farletuzumab ecteribulin (MORAb-202) | FRα | Ecteribulin (MTi) 4 |
Bristol-Myers Squibb | Phase II ongoing | Phase I: First in human (NCT04300556) [28], Expansion PROC [27] Phase II: NCT05613088 |
| Levultemab tazevibulin (STRO-002) | FRα | Hemasterlin (MTi) 4 |
Sutro Biopharma | FDA Fast track, Phase III trial recruiting | Phase I: STRO-002-GM1 [23] Phase II/III trial REFRaME-01 [24] |
| Rinatabart sesutecan (PRO1184) | FRα | Exatecan (Ti) 8 |
Profound Bio | FDA fast track, Phase I/II ongoing | Phase I/II: NCT05579366 |
| BAT8006 | FRα | NR (Ti) 8 |
Bio-Thera Solutions | Phase I ongoing China Only | Phase I: NCT05378737 |
| IMGN151 | FRα | DM21 (MTi) 3.5 |
Immunogen | Phase I ongoing | Phase I: NCT05527184 |
| AZD5335 | FRα | TOP1i (Ti) 8 |
AstraZeneca | Phase I/II ongoing | Phase I/II: NCT05797168 |
| LY4170156 | FRα | Exatecan (Ti) 8 |
Eli Lilly and Company | Phase I ongoing | Phase I: NCT06400472 |
| DB-1305 | Trop-2 | P1021 (Ti) 4 |
DualityBio Inc. | FDA Fast Track | Phase I/II: NCT05438329 |
| Sacituzimab govitecan | Trop-2 | SN-38 (Ti) 7 |
Gilead Sciences | Phase II ongoing | Phase II: NCT04251416 |
| Datopotomab deruxtecan | Trop-2 | Deruxtecan (Ti) 4 |
AztraZeneca | Phase II ongoing | Phase II: NCT05489211 (TROPION-PanTumor03) |
| Sacituzumab tirumotecan (MK-2870) |
Trop-2 | Belotecan-derivative (Ti) 7.4 |
Merck Sharp & Dohme | Phase I/II ongoing | Phase I/II: NCT04152499 |
| TORL-1-23 | CLDN6 | MMAE (MTi) 4 |
TORL Biotherapeutics | Phase I ongoing | Phase I: NCT05103683 |
| Raludotatug deruxtecan | CDH6 | Deruxtecan (Ti) 8 |
Daiichi Sankyo | Phase II/III ongoing | Phase I: NCT04707248 Phase II/III: NCT06161025 |
| CUSP06 | CDH6 | Exatecan (Ti) 8 |
OnCusp Therapeutics | Phase I ongoing | Phase I: NCT06234423 |
| LY4101174 | Nectin-4 | Exatecan (Ti) 8 |
Eli Lilly and Company | Phase I ongoing | Phase I: NCT06400472 |
| TUB-040 | NaPi2b | Exatecan (Ti) 8 |
Tubulis GmbH | FDA fast track Phase I/II ongoing |
Phase I/II: NCT06303505 (NAPISTAR 1-01) |
| HS-20089 | B7-H4 | (Ti) 6 |
Hansoh BioMedical R&D | Phase II ongoing China only | Phase I: NCT05194072 Phase II: NCT06014190 |
| AZD8205 | B7-H4 | TOP1i (Ti) 8 |
AztraZeneca | Phase I/II ongoing | Phase I/II: NCT05123482 |
| RC88 | MSLN | MMAE (Ti) 4 |
RemeGen Co. | FDA fast track designation for PROC | Phase I/II: NCT04175847 Phase II: NCT06173037 |
| Endometrial | |||||
| Trastuzumab duocarmazine (SYD985) | HER2 | Duocarmycin (AA) 3 |
Byondis B.V. | Phase II ongoing | Phase II: NCT04205630 |
| DB-1303 | HER2 | P1003 (Ti) 8 |
DualityBio | FDA breakthrough designation | Phase I/II: NCT05150691 |
| IMGN151 | FRα | DM21 (MTi) 3.5 |
Immunogen | Phase I ongoing | Phase I: NCT05527184 |
| LY4170156 | FRα | Exatecan (Ti) 8 |
Eli Lilly and Company | Phase I ongoing | Phase I: NCT06400472 |
| Sacituzimab govitecan | Trop-2 | SN-38 (Ti) 7 |
Gilead Sciences | Phase II ongoing | Phase II: NCT04251416 |
| Sacituzumab tirumotecan (MK-2870) |
Trop-2 | Belotecan-derivative (Ti) 7.4 |
Merck Sharp & Dohme | Phase III recruiting | Phase III: NCT06132958 |
| Datopotomab deruxtecan | Trop-2 | Deruxtecan (Ti) 4 |
AztraZeneca | Phase II ongoing | Phase II: NCT05489211 (TROPION-PanTumor03) |
| AZD8205 | B7-H4 | TOP1i (Ti) 8 |
Aztrazeneca | Phase I/II ongoing | Phase I/II: NCT05123482 |
| HS-20089 | B7-H4 | (Ti) 6 |
Hansoh BioMedical R&D | Phase II ongoing China only | Phase I: NCT05194072 Phase II: NCT06014190 |
| SGN-B7H4V | B7-H4 | MMAE (MTi) 4 |
Seagen Inc. | Phase I ongoing | Phase I: NCT05194072 |
| LY4101174 | Nectin-4 | Exatecan (Ti) 8 |
Eli Lilly and Company | Phase I ongoing | Phase I: NCT06400472 |
| Cervical | |||||
| Tisotumab vedotin | TF | MMAE (MTi) 4 |
Seagen Inc. | FDA approved, 2L r/m CC | Phase II: InnovaTV 204 trial [48▪] Phase III: InnovaTV301 [49▪▪,50▪] Ongoing trials: phase 1b/II: innovaTV 205 [51] |
| LY4101174 | Nectin-4 | Exatecan (Ti) | Eli Lilly and Company | Phase I ongoing | Phase I: NCT06400472 |
| Sacituzimab govitecan | Trop-2 | SN-38 (Ti) 7 |
Gilead Sciences | Phase II ongoing | Phase II: NCT05838521 |
| Sacituzumab tirumotecan (MK-2870) |
Trop-2 | Belotecan-derivative (Ti) 7.4 |
Merck Sharp & Dohme | Phase III recruiting | Phase II: NCT05642780 Phase III: NCT06459180 |
| RC88 | MSLN | MMAE (Ti) 4 |
RemeGen Co. | Phase I/II ongoing | Phase I/II: NCT04175847 |
AA, alkylating agent; ADC, antibody–drug conjugate; CDH6, cadherin-6; CLDN6, claudin-6; DAR, drug-antibody ratio; DM4, N20-deacetyl-N20-(4-mer-capto-4-methyl-1-oxopentyl)-maytansin; FDA, Food and Drug Administration; FRα, folate receptor alpha; MMAE, monomethyl auristatin E; MSLN, mesothelin; MTi, microtubule inhibitor; NR, not reported; PROC, platinum-resistant ovarian cancer; PSOC, platinum-sensitive ovarian cancer; TF, tissue factor; Ti, topoisomerase inhibitor; Trop-2, trophoblast cell surface antigen-2.