Table 2.
Positive phase II/III trials of antibody–drug conjugates in haematological malignancies leading to FDA approval.
| Drug | FDA Approval |
Pivotal Trial(s) | Population | Number of Patients | Antibody Target, Linker and Payload | Results of Intervention vs. Comparator |
|---|---|---|---|---|---|---|
| Gemtuzumab ozogamicin (GO) | 2017 | ALFA-0701 [81,82,83] (phase III) | Newly diagnosed, CD33+ AML, age 50–70. | GO + standard therapy: 140 SOC: 140 |
Ab target: CD33 Linker: hydrazone (cleavable) Payload: calicheamicin |
2 yr EFS 40.8% vs. 17.1%, RFS 50.3% vs. 22.7%. |
| 2017 | AAML0531 [84] (phase III) |
Newly diagnosed AML age 0–29 years. | GO + standard therapy: 511 SOC: 511 |
3 yr EFS 53.1% vs. 46.9%, 3 yr OS 69.4% vs. 65.4%. | ||
| 2017 | AML-19 [85] (phase III) | Newly diagnosed AML, >75 yrs or 61–75 yrs and unfit for intensive chemotherapy. | GO: 118 BSC: 119 |
mOS 4.9 vs. 3.6 mths. | ||
| 2017 | MyloFrance-1 [86] (phase II) |
CD33+ AML in first relapse. | GO: 57 (single arm) |
ORR 33.3%, mOS 8.4 mths, mRFS 11.0 mths. | ||
|
Brentuximab vedotin
(BV) |
2018 | ECHELON-2 [87] (phase III) |
Untreated CD30+ peripheral T cell lymphomas. | BV + CHP: 226 CHOP: 226 |
Ab target: CD30 Linker: mc-VC-PABC (cleavable) Payload: MMAE |
5 yr PFS 51.4% vs. 43.0%, 5 yr OS 70.1% vs. 61.0%. |
| 2018 | ECHELON-1 [88] (phase III) |
Untreated stage III-IV classical Hodgkin lymphoma. | BV + AVD: 664 ABVD: 670 |
5 yr PFS 82.2% vs. 75.3%, OS immature. | ||
| 2017 | ALCANZA [89] (phase III) |
Relapsed primary cutaneous anaplastic large cell lymphoma or CD30+ mycosis fungoides. | BV: 64 TPC: 64 |
ORR 54.7% vs. 12.5%, mPFS 16.7 vs. 3.5 mths, 3 year OS 64.4% vs. 61.9%. | ||
| Polatuzumab vedotin (PV) | 2019 | Study GO29365 [90] (phase Ib/II) |
Relapsed or refractory DLBCL with ≥2 prior therapies. | 1. PV + BG: 20 2. PV + BR: 40 3. BR: 40 |
Ab target: CD79b Linker: mc-VC-PABC (cleavable) Payload: MMAE |
Phase I: PV + BG mOS 10.8 mths. Phase II: PV + BR vs. BR mPFS 12.4 vs. 4.7 mths. |
| Belantamab mafodotin (BM) | 2020 | DREAMM-2 [25] (phase II) |
Relapsed or refractory multiple myeloma with ≥4 prior therapies. |
Cohort 1 (BM 2.5 mg/kg): 97 Cohort 2 (BM 3.4 mg/kg): 99 |
Ab target: BCMA Linker: mc (non-cleavable) Payload: MMAF |
Cohort 1: ORR 31%, mPFS 2.9 mths. Cohort 2: ORR 34%, mPFS 4.9 mths. |
| Inotuzumab ozogamicin (InO) | 2017 | INO-VATE [91] (phase III) |
Relapsed or refractory B-cell precursor ALL. | InO: 164 TPC: 162 |
Ab target: CD22 Linker: hydrazone (cleavable) Payload: calicheamicin |
mOS: 7.7 vs. 6.2 mths, 2 yr OS: 22.8% vs. 10.0%. |
|
Moxetumomab
pasudotox (MP) |
2018 | Study 1503 [92] (phase II) |
Relapsed or refractory hairy cell leukaemia. | MP: 80 (single arm) |
Ab target: CD22 Linker: hydrazone (cleavable) Payload: pasudotox |
Durable CR rate of 36%, median CR duration 62.8 mths, mPFS 41.5 mths. |
|
Loncastuximab tesirine
(LT) |
2021 | LOTIS-2 [93] (phase II) |
Relapsed or refractory DLBCL after ≥2 therapies. | LT: 145 (single arm) |
Ab target: CD19 Linker: valine–alanine (cleavable) Payload: PBD dimer |
ORR 48.3%, mPFS 4.9 mths, mOS 9.9 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; MMAE/F, monomethyl auristatin-E/F; mth, months; mPFS, median progression free survival; mOS, median overall survival; mths, months; NACT, neoadjuvant chemotherapy; NMPA, National Medical Products Administration of China; ORR, objective response rate; PBD, pyrrolobenzodiazepine; PD, progressive disease; RFS, relapse-free survival; SOC, standard of care; 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; yr, years.