Table 2.
Summary of recruiting phase III trials examining approved ADCs.
| ADC | NCT number (study name) | Conditions | Study arms and interventions (according to available data registered in clinicaltrials.gov, a: active comparator, b: experimental arm) |
|---|---|---|---|
| GO (Mylotarg®, CMA-676) | NCT02724163 (Myechild01) | AML in children | GO dose-finding study: Cohort 1: 3 mg/m2 IV on D4; Cohort 2: 3 mg/m2 IV on D4 and 7, Cohort 3: 3 mg/m2 IV on D4, 7 and 10. A single GO dose will be compared with the optimum tolerated number of doses when combined with induction chemotherapy.Parallel assignments include the comparison of mitoxantrone with cytarabine versus daunorubicin and cytarabine, high-dose cytarabine versus fludarabine and cytarabine as consolidation regimens and conventional myeloablative conditioning with busulfan and cyclophosphamide versus reduced intensity conditioning with fludarabine and busulfan. |
| NCT02665065 | R/R AML | (a) Conventional care including: GO, azacytidine, carboplatin, cladribine, clofarabine, cyclophosphamide, cytarabine, daunorubicin, decitabine, doxorubicin, enasidenib, etoposide, fludarabine, idarubicin, ivosidenib, l-asparaginase, midostaurin, mitoxantrone, sorafenib, thioguanine, topotecan, venetoclax(b) Lomab-B with a reduced intensity conditioning regimen containing fludarabine and low-dose total body irradiation prior to hematopoietic cell transplantation | |
| NCT02272478 (AML18) | AML in patients over 60 years of age | There are five randomized comparisons within the trial:Course 1:(1) Patients not known to have adverse risk cytogenetics receive either DC plus GO or CPX-351(2) Patients who received DC but did not achieve complete remission or who are MRD+ receive either DC or DC plus cladribine or fludarabine, high dose cytarabine, idarubicin and granulocyte colony-stimulating factorCourse 2:(3) All patients who received DC are allocated AC220 or no AC220. Those receiving AC220 are subsequently randomized to with or without maintenance for 1 year (4) Patients in complete remission after course 2 are randomized to DC versus intermediate dose cytarabine (5) Patients who received CPX-351 and are not in complete remission or who are MRD+ are administered either CPX-351 according to course 1 schedule or standard dose CPX-351 | |
| BV | NCT02661503 | Newly diagnosed, previously untreated advanced classic HL | (a) Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone for 4–6 cycles (21 days)(b) BV, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, dexamethasone for 4–6 cycles (21 days) |
| NCT03907488 | Newly diagnosed, previously untreated advanced classic HL | (b) Arm I: doxorubicin IV, vinblastine IV, dacarbazine IV, nivolumab IV on D1, 15. Patients may receive pegfilgrastim SC on D2, 16 or filgrastim SC/IV on D5–10, 20–25 for adults and D4–9 for pediatric patients for 6 28-day cycles. After completion of cycle 6, patients may receive radiation therapy 5 days per week for 4 weeksArm II: doxorubicin IV, vinblastine IV, dacarbazine IV, BV IV on D1, 15. Patients may receive pegfilgrastim SC on D2, 16 or filgrastim SC/IV on D5–10, 20–25 for adults and D4–9 for pediatric patients for 6 28-day cycles. After completion of cycle 6, patients may receive radiation therapy 5 days per week for 4 weeks | |
| Ado-trastuzumab emtansine (T-DM1, Kadcyla®) | NCT03975647 (HER2CLIMB-02) | HER2+ locally advanced or metastatic breast cancer previously treated with a taxane and trastuzumab | (a) Placebo plus trastuzumab emtansine(b) Tucatinib plus trastuzumab emtansine |
| NCT03529110 (DESTINY-Breast03) | HER2+ locally advanced or metastatic breast cancer previously treated with a taxane and trastuzumab | (a) Trastuzumab emtansine(b) Trastuzumab deruxtecan | |
| InO (Besponsa®,CMC-544) | NCT03150693 | Newly diagnosed precursor B-cell acute lymphoblastic leukemia in young adults (<40 years old) | (a) Remission consolidation chemotherapy: Cyclophosphamide IV, cytarabine IV, mercaptopurine PO, vincristine IV, pegylated L-asparaginase IV and methotrexate IT Interim maintenance chemotherapy: Vincristine IV, methotrexate IV and IT and pegylated L-asparaginase IV. Rituximab IV in CD20+ subjects. Delayed intensification: Vincristine IV, dexamethasone PO, doxorubicin IV, pegylated L-asparaginase IV, cyclophosphamide IV, cytarabine IV, thioguanine PO and methotrexate IV. Rituximab IV in CD20+ subjects. Maintenance therapy: Vincristine IV, dexamethasone PO and mercaptopurine PO, methotrexate IT(b) Patients undergo all prior courses including InO |
| NCT03913559 | High-risk B-cell acute lymphoblastic leukemia, mixed phenotype acute leukemia, B-lymphoblastic lymphoma | Induction: cytarabine IT, vincristine IV, daunorubicin IV, pegasparase IM/IV and methotrexate IT for 5 weeks. Patients <10 years old receive dexamethasone PO/IV and patients >10 years old receive prednisone PO/IV. Consolidation: cyclophosphamide IV, cytarabine IV/SC, mercapturine PO, methotrexate IT, vincristine IV and pegasparase IV/IM for 8 weeksPost consolidation; High-risk B-ALL(a) Interim maintenance: vincristine IV, methotrexate IV, leucovorin PO, mercapturine PO, methotrexate IT for 9 weeks. Delayed intensification part 1: Methotrexate IT, dexamethasone PO/IV, vincristine IV, doxorubicin IV, pegasparase IV/IM for 8 weeks (part I and II). Delayed intensification part 2: cyclophosphamide IV, thioguanine PO, cytarabine IV/SC, methotrexate IT, vincristine IV and pegaspargase IV/IM. Interim maintenance: Vincristine IV, methotrexate IV, methotrexate IT, pegapsargase IV/IM for 8 weeks. Maintenance: Vincristine IV, prednisolone PO/IV, mercapturine PO, methotrexate PO and methotrexate IT every 12 weeks for up to 2 years.(b) InO, methotrexate IT for 4 weeks. Interim maintenance: Vincristine IV, methotrexate IV, leucovorin PO/IV, mercapturine PO and methotrexate IT for 9 weeks. Delayed intensification I: Methotrexate IT, dexamethasone PO/IV, vincristine IV, doxorubicin IV and pegasparase IV/IM for 8 weeks (part I and II). Delayed intensification II: Cyclophosphamide IV, thioguanine PO, cytarabine IV/SC, methotrexate IT, vincristine IV and pegaspargase IV/IM. Interim maintenance: Vincristine IV, methotrexate IV, methotrexate IT, pegaspargase IV/IM for 8 weeks. Maintenance as in control armParallel assignments include experimental regimes (InO not included) for High-risk favorable B-ALL, mixed phenotype acute leukemia and B-lymphoblastic lymphoma | |
| PV (Polivy®, DCDS4501A, RG7596) | NCT03274492 (POLARIX) | Previously untreated DLBCL | (a) Placebo, rituximab IV, doxorubicin IV, cyclophosphamide IV, vincristine IV on D1 and prednisone PO ond D1–5 of 21-day cycle for 6 cycles and rituximab IV as monotherapy in cycles 7–8(b) PV, placebo for vincristine IV, cyclophosphamide IV, doxorubicin IV on D1, prednisone PO on D1–5 of 21-day cycle for 6 cycles, rituximab IV as monotherapy for cycles 7, 8 |
| NCT04182204 (POLARGO) | R/R DLBCL | (a) Rituximab IV on D1, gemcitabine IV and oxaliplatin IV on D2 of 21-day cycles for a maximum of 8 cycles(b) Safety run-in stage (stage 1): 10 patients receive PV IV, rituximab IV on D1, gemcitabine and oxaliplatin on D2 of 21-day cycles for a maximum of 8 cycles.Stage 2: All patients receive PV IV, rituximab IV on D1, gemcitabine and oxaliplatin on D2 of 21-day cycles for a maximum of 8 cycles | |
| EV (Padcev®, AGS-22M6E, AGS-22CE) | NCT04223856 (EV-302) | Untreated locally advanced or metastatic urothelial cancer | (a) Gemcitabine plus cisplatin or carboplatin(b) EV + pembrolizumabEV + pembrolizumab + cisplatin or carboplatin |
| Fam-trastuzumab deruxtecan-nxki (Enhertu®, DS-8201a) | NCT03523585 (DESTINY-Breast02) | Previously treated HER2+ advanced or metastatic breast cancer | (a) Trastuzumab plus capecitabine or lapatinib plus capecitabine(b) Trastuzumab deruxtecan |
| NCT03529110 (DESTINY-Breast03) | HER2+ locally advanced or metastatic breast cancer previously treated with a taxane and trastuzumab | (a) Trastuzumab emtansine(b) Trastuzumab deruxtecan | |
| NCT03734029 (DESTINY-Breast04) | Previously treated HER-low advanced or metastatic breast cancer | (a) Capecitabine, eribulin, gemcitabine, paclitaxel, nab-paclitaxel(b) Trastuzumab deruxtecan | |
| Sacituzumab govitecan-hziy (Trodelvy® IMMU-132, HRS7-SN38) | NCT03901339 (TROPICS-02) | Metastatic or locally recurrent inoperable HR+/HER2− breast cancer, after failure of at least 2, and no more than 4, prior chemotherapy regimens for metastatic disease | (a) Eribulin, capecitabine, gemcitabine, vinorelbine(b) Sacituzumab govitecan |
ADC, antibody–drug conjugate; AML, acute myeloid leukemia; BV, brentuximab vedotin; DLBCL, diffuse large B-cell lymphoma; DC, daunorubicin, cytarabine; EV, enfortumab vedotin-ejfv; GO, gemtuzumab ozogamicin; HL, Hodgkin’s lymphoma; IM, intramuscular; InO, inotuzumab ozogamicin; IT, intrathecal; IV, intravenous; MRD, minimal residual disease; NCT, ClinicalTrials.gov identifier; PO, per os; PV, polatuzumab vedotin-piiq; R/R, relapsed or refractory; SC, subcutaneously.