Table 5 Summary of clinical trials investigating the combination of ADCs and targeted therapy
From: The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors
Target | NCT number | Other names | Drug | Partner drugs | Partner drug category (target) | Phase | Start | Treatment setting | Efficacy | |
|---|---|---|---|---|---|---|---|---|---|---|
HER2 | NCT01120184 [72] | MARIANNE | T-DM1 | Pertuzumab | Anti-HER2 mAb | III | 2010 | mBC | Positive | |
Taxane | CT | |||||||||
NCT03225937 [73] | HERACLES | T-DM1 | Pertuzumab | Anti-HER2 mAb | II | 2012 | mCRC | Negative | ||
NCT02073916 [20] | STELA | T-DM1 | Lapatinib + Abraxane | EGFR/HER2 TKI + CT | I | 2013 | mBC | Positive | ||
NCT01983501 [74] | NA | T-DM1 | Tucatinib | HER2 inhibitor | Ib | 2014 | mBC | Positive | ||
NCT02038010 [75] | NA | T-DM1 | BYL719 (alpelisib) | PI3Kα inhibitor | I | 2014 | mBC | Positive | ||
NCT02073487 [21] | TEAL | T-DM1 | Lapatinib + Abraxane | EGFR/HER2 TKI + CT | II | 2014 | Neoadjuvant, BC | Positive | ||
NCT02657343 [76] | NA | T-DM1 | Ribociclib | CDK4/6 inhibitor | Ib/II | 2016 | mBC | Negative | ||
NCT03364348 (completed) | NA | T-DM1 | Utomilumab | T cell co-stimulatory receptor agonist (4-1BB) | I | 2017 | mBC | NA | ||
NCT03523572 [77] | NA | T-DXd | Nivolumab | IO | I | 2018 | mBC & mUC | Positive | ||
NCT04042701 [78] | NA | T-DXd | Pembrolizumab | IO | I | 2019 | mBC & mNSCLC | NA | ||
NCT03975647 [79] | HER2CLIMB-02 | T-DM1 | Tucatinib | HER2 inhibitor | III | 2019 | mBC | NA | ||
NCT04264936 [80] | NA | RC48 | Toripalimab (JS001) | IO | Ib/II | 2020 | mUC | Positive | ||
NCT04235101 (completed) | NA | (Vic-)trastuzumab duocarmazine (SYD985) | Niraparib | PARP inhibitor | I | 2020 | Advanced solid tumors | NA | ||
NCT04538742 [81] | Destiny Breast 07 | T-DXd | Pertuzumab | HER2 mAb | Ib/II | 2020 | mBC | NA | ||
Paclitaxel | CT | |||||||||
Durvalumab | IO | |||||||||
Tucatinib | HER2 inhibitor | |||||||||
NCT04556773 (active, not recruiting) | Destiny Breast 08 | T-DXd | Anastrozole | ET | Ib/II | 2020 | mBC | NA | ||
Capivasertib | Akt inhibitor | mBC | ||||||||
Fulvestrant | ET | mBC | ||||||||
NCT04539938 [82] | HER2CLIMB-04 | T-DXd | Tucatinib | HER2 inhibitor | II | 2020 | mBC | NA | ||
NCT04197687 (recruiting) | NA | T-DM1 | TPIV100 + Sargramostim | HER2 vaccine + GM-CSF | II | 2020 | Adjuvant BC | NA | ||
Sargramostim | GM-CSF | |||||||||
NCT04704661 (recruiting) | DASH | T-DXd | AZD6738 | ATR inhibitor | I | 2021 | Advanced solid tumors | NA | ||
NCT04983121 (recruiting) | NA | ARX788 | Pyrotinib Maleate | Pan-ErbB TKI | II | 2021 | Neoadjuvant, BC | NA | ||
NCT04585958 (recruiting) | NA | T-DXd | Olaparib | PARP-1/2 inhibitor | I | 2021 | mEC | NA | ||
NCT05372614 (recruiting) | NA | T-DXd | Neratinib | Pan HER inhibitor | I | 2022 | Advanced solid tumors | NA | ||
NCT05426486 (recruiting) | NA | ARX788 | Pyrotinib | Pan-ErbB TKI | II/III | 2022 | Neoadjuvant, BC | NA | ||
NCT05868226 (recruiting) | PRE-I-SPY-PI | T-DXd | ALX148 | CD47-blocking fusion protein | I | 2022 | mBC | NA | ||
TROP2 | NCT04039230 [83] | NA | SG | Talazoparib | PARP inhibitor | I/II | 2019 | mBC | Positive | |
NCT04381832 (active, not recruiting) | NA | SG | Etrumadenant + Zimberelimab | Dual adenosine receptor antagonist + IO | I/II | 2020 | mCRPC | NA | ||
Etrumadenant | Dual adenosine receptor antagonist | |||||||||
NCT05143229 (recruiting) | ASSET | SG | Alpelisib | Specific Pi3K inhibitor | I | 2021 | mBC | NA | ||
NCT05006794 (recruiting) | NA | SG | GS9716 | MCL-1 antagonist | I | 2021 | Advanced solid tumors | NA | ||
NCT05575804 (active, not recruiting) | NA | GQ1001 | Pyrotinib | Pan-ErbB TKI | I/II | 2022 | mBC | NA | ||
Nectin-4 | NCT04724018 [84] | NA | EV | SG | ADC | I | 2021 | mUC | NA | |
NCT04878029 (recruiting) | NA | EV | Cabozantinib | MET, RET, AXL, VEGFR2, FLT3, and c-KIT TKI | I | 2021 | mUC | NA | ||
NCT03606174 (terminated due to sponsor decision) | NA | EV | Sitravatinib | TYRO3, AXL MER, VEGFR2 and KIT TKI | II | 2018 | mUC | NA | ||
NCT04963153 (recruiting) [25] | NA | EV | Erdafitinib | FGFR inhibitor | I | 2021 | Metastatic bladder cancer | NA | ||
FRα | NCT05200364 [85] | NA | STRO-002 | BEV | Anti-VEGF mAb | I | 2022 | Advanced Epithelial Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) | NA | |
NCT05445778 (recruiting) | NA | Mirvetuximab soravtansine | BEV | Anti-VEGF mAb | III | 2022 | Advanced Epithelial Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) | NA | ||
NA | AZD5305 | PARP1 inhibitor | ||||||||
GLORIOSA | Durvalumab + AZD5305 | IO + PARP1 inhibitor | ||||||||
NA | 5-FU + LV + BEV or Capecitabine + BEV | CT + Anti-VEGF mAb | ||||||||
MET | NCT02099058 [86] | NA | Telisotuzumab vedotin (ABBV-399) | Osimertinib | EGFR TKI | I/Ib | 2014 | Advanced solid tumors | NA | |
NA | Erlotinib | HER2 mAb | Positive | |||||||
NA | Nivolumab | IO | Negative | |||||||
EGFR-cMET bispecific | NCT05647122 (recruiting) | EGRET | AZD9592 | Osimertinib | EGFR TKI | I | 2022 | Advanced solid tumors | NA | |
LIV-1 | NCT01969643 [87] | NA | Ladiratuzumab vedotin | Trastuzumab | Anti-HER2 mAb | I | 2013 | mBC | Â | |
B7-H3 | NCT05293496 (recruiting) | NA | MGC018 | Lorigerlimab | Bispecific IgG4 DART | I | 2022 | Advanced solid tumors | NA | |