Table 1.
Positive phase II/III trials of antibody–drug conjugates in solid tumours leading to FDA approval.
| Drug | FDA Approval | Pivotal Trial(s) | Population | Number of Patients |
Antibody Target, Linker and Payload | Results of Intervention vs. Comparator |
|---|---|---|---|---|---|---|
|
Trastuzumab emtansine
(T-DM1) |
2013 | EMILIA [64] (phase III) |
Advanced HER2+ breast cancer with PD after trastuzumab + taxane. | T-DM1: 495 Capecitabine + lapatinib: 496 |
Ab target: HER2 Linker: SMCC (non-cleavable) Payload: DM1 |
ORR 43.6% vs. 30.8%, mPFS 9.6 vs. 6.4 mths, mOS 30.9 vs. 25.1 mths. |
| 2019 | KATHERINE [65] (phase III) |
Early-stage HER2+ breast cancer with residual disease after NACT. | T-DM1: 743 Trastuzumab: 743 |
3 yr iDFS 88.3% vs. 77.0%. | ||
|
Trastuzumab deruxtecan
(T-DXd) |
2022 | DESTINY-Breast03 [66] (phase III) |
Advanced HER2+ breast cancer with PD after trastuzumab + taxane. | T-DXd: 261 T-DM1: 263 |
Ab target: HER2 Linker: GGFG tetrapeptide (cleavable) Payload: Deruxtecan |
ORR 79.7% vs. 34.2%, mPFS not reached vs. 6.8 mths with T-DM1, mOS both not reached. |
| 2022 | DESTINY-Breast02 [67] (phase III) |
Advanced HER2+ breast cancer with PD after T-DM1. | T-DXd: 406 TPC: 202 |
ORR 70% vs. 29%, mPFS 17.8 vs. 6.9 mths, mOS 39.2 vs. 26.5 mths. |
||
| 2022 | DESTINY-Breast04 [68] (phase III) |
Advanced HER2 low breast cancer with PD after 1–2 lines of chemotherapy. | T-DXd: 373 TPC: 184 |
ORR 52.3% vs. 16.3%, mPFS 9.9 vs. 5.1 mths, mOS 23.4 vs. 16.8 mths. |
||
| 2021 | DESTINY-Gastric01 [69] (phase II) |
Advanced HER2+ gastric/GOJ cancers after ≥2 lines of therapy. | T-DXd: 125 TPC: 62 |
ORR 51% vs. 14%, mPFS 5.6 vs. 3.5 mths, mOS 12.5 vs. 8.4 mths. |
||
| 2022 | DESTINY-Lung01 [70] (phase II) | Advanced HER2+ NSCLC refractory to standard therapy. | T-DXd: 91 (single arm) | ORR 55%, mPFS 8.2 mths, mOS 17.8 mths. |
||
|
Sacituzumab govitecan
(SG) |
2023 | TROPiCS-02 [71] (phase III) | Advanced HR+ breast cancer, HER2- or low with PD after ET and ≥2 systemic therapies. | SG: 272 TPC: 271 |
Ab target: Trop-2 Linker: CL2A (cleavable) Payload: SN-38 |
ORR 21% vs. 14%, mPFS 5.5 vs. 4.0 mths, mOS 13.9 vs. 12.3 mths. |
| 2020 | ASCENT [72] (phase III) |
Advanced TNBC with PD after ≥2 lines of chemotherapy. | SG: 235 TPC: 233 |
ORR 35% vs. 5%, mPFS 5.6 vs. 1.7 mths, mOS 12.1 vs. 6.7 mths. |
||
| 2021 | TROPHY [73] (phase II) |
Advanced urothelial cancer with PD after platinum and immunotherapy. | SG: 113 (single arm) |
ORR 27%, mPFS 5.4 mths, mOS 10.9 mths. |
||
| 2020 | IMMU-132-01 [74] (phase I/II) | Advanced TNBC after ≥2 lines of chemotherapy. | SG: 108 (single arm) |
ORR 33.3%, mPFS 5.5 mths, mOS 13.0 mths. |
||
|
Enfortumab vedotin
(EV) |
2019 | EV-201 [75,76] (phase II) | Advanced urothelial carcinoma. Cohort 1: PD after platinum + immunotherapy. Cohort 2: PD after immunotherapy, no prior platinum. |
Cohort 1: 125 Cohort 2: 89 (single arm) |
Ab target: Nectin-4 Linker: mc-VC-PABC (cleavable) Payload: MMAE |
Cohort 1: ORR 44%, mPFS 5.8 mths, mOS 11.7 mths Cohort 2: ORR 52%, mPFS 5.8 mths, mOS 14.7 mths. |
| 2019 | EV-301 [77] (phase III) | Advanced urothelial carcinoma with PD after platinum and immunotherapy. | EV: 301 TPC: 307 |
ORR 40.6% vs. 17.9%, mPFS 5.6 vs. 3.7 mths, mOS 12.9 vs. 9.0 mths. |
||
|
Disitamab vedotin *
(DV) |
2021 | [78] (phase II) |
Advanced HER2+ urothelial carcinoma with PD after ≥1 prior therapy. | DV: 43 (single arm) |
Ab target: HER2 Linker: mc-VC-PABC (cleavable) Payload: MMAE |
ORR 51.2%, mPFS 6.9 mths, mOS 13.9 mths. |
|
Tisotumab vedotin
(TV) |
2021 | InnovaTV 204 [79] (phase II) | Recurrent/advanced cervical cancer with PD after ≤2 lines of chemotherapy. | TV: 102 (single arm) |
Ab target: tissue factor Linker: mc-VC-PABC (cleavable) Payload: MMAE |
ORR 24%, mPFS 4.2 mths, mOS 12.1 mths. |
| Mirvetuximab soravtansine (MIRV) | 2022 | SORAYA [80] (phase II) |
FRα high platinum-resistant ovarian cancer with ≤3 prior systemic therapies, including bevacizumab. | MIRV: 106 (single arm) |
Ab target: FRα Linker: disulfide hydrophilic sulfo-SPDB (cleavable) Payload: DM4 |
ORR 32.4%, mPFS 4.3 mths, mOS 13.8 mths. |
Abbreviations: Ab, antibody; ABVD, doxorubicin, bleomycin, vinblastine, and dacarbazine; ALL, acute lymphoblastic leukaemia; AML, acute myeloid leukaemia; AVD, doxorubicin, vinblastine, and dacarbazine; BCMA, B-cell maturation antigen; BG, bendamustine and obinutuzumab; BR, bendamustine and rituximab; BSC, best supportive care; CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; CHP, cyclophosphamide, doxorubicin, and prednisone; CL2A, cross-linked 2A; CR, complete response; DLBCL, diffuse large B cell lymphoma; EFS, event-free survival; FRα, folate receptor α; GGFG, Gly-Gly-Phe-Gly; HR, hormone receptor; mc-VC-PABC, maleimidocaproyl-valyl-citrullinyl-p-aminobenzyloxycarbonyl; iDFS, invasive disease free survival; MMAE/F, monomethyl auristatin-E/F; mths, months; mPFS, median progression free survival; mOS, median overall survival; NACT, neoadjuvant chemotherapy; NMPA, National Medical Products Administration of China; ORR, objective response rate; PBD, pyrrolobenzodiazepine; PD, progressive disease; RFS, relapse-free survival; SG, sacituzumab govitecan; SMCC, succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate; SPDB, N-succinimydl 4-(2-pyridyldithio)−2-sulfobutanoate); TPC, treatment of physician’s choice. * Approved by NMPA.