Table 3.
Antibody-drug conjugates under development for patients with HER2-positive breast cancer in clinical trials as of February 2023
| ADC | Antibody | Payload | Linker | Average DAR | Sponsor | Indications | Phase (status) | NCT identifier |
|---|---|---|---|---|---|---|---|---|
| A166 | humanized IgG1 (trastuzumab) | duostatin-5 (Duo-5; MMAF derivative) | cleavable (valine-citrulline) | 2.0 | Fudan University | HER2-positive patients with refractory unresectable locally advanced or metastatic breast cancer who have failed previous ADC drug therapy | II (not yet recruiting) | NCT05346328 |
| Klus Pharma | patients with relapsed/refractory cancers expressing the HER2 antigen or having amplified the her2 gene, including HER2-positive breast cancer | I/II (active, not recruiting) | NCT03602079 | |||||
| Sichuan Kelun Pharmaceutical Research Institute | patients with unresectable, locally advanced or metastatic HER2-expressing solid tumors, including breast cancer | I (recruiting) | NCT05311397 | |||||
| – | patients with HER2-expressing locally advanced or metastatic solid tumors, including HER2-positive breast cancer | I | CTR20181301 | |||||
| LCB14-0110 (FS-1502) | trastuzumab | MMAF | cleavable (β-glucuronide) | 2.0 | Shanghai Fosun Pharmaceutical Industrial Development | patients with HER2-expressing advanced malignant solid tumors (phase Ia) and patients with metastatic HER2-positive breast cancer (an expanded cohort; phase Ib) to evaluate the ADC in patients with metastatic, HER2-positive breast cancer | I (recruiting) | NCT03944499 |
| ALT-P7 | trastuzumab biobetter (HM2) | MMAE | cleavable | 2.0 | Alteogen | patients with HER2-positive metastatic breast cancer who have progressed on previous trastuzumab-based therapy | I (completed) | NCT03281824 |
| ADCT-502 | an engineered version of trastuzumab | tesirine (a PBD-based dimer (SG3249)) | cleavable (valine-alanine) | 1.7 | ADC Therapeutics | patients with advanced solid tumors, including HER2-positive breast cancer | I (terminated) | NCT03125200 |
| BAT8001 | trastuzumab biosimilar (BAT0606) | a maytansine derivative | non-cleavable (6-maleimidocaproic acid) | – | Bio-Thera Solutions | patients with HER2-positive advanced breast cancer | III (unknown) | NCT04185649 |
| Bio-Thera Solutions | patients with HER2-positive advanced solid tumors (BAT8001 in combination with BAT1306) | I/IIa (unknown) | NCT04151329 | |||||
| Bio-Thera Solutions | patients with HER2-positive solid tumors (breast cancer or gastric cancer) | I (unknown) | NCT04189211 | |||||
| trastuzumab duocarmazine (SYD985) | humanized IgG1 (with the same amino acid sequence as trastuzumab) | seco-DUBA (the duocarmycin prodrug) | cleavable (valine-citrulline) | 2.8 | Byondis | patients with HER2-positive locally advanced or metastatic breast cancer (SYD985 versus TPC) | III (active, not recruiting) | NCT03262935 |
| Byondis | patients with HER2-expressing locally advanced or metastatic solid tumors (the single arm part of the trial) and patients with locally advanced or metastatic HER2-positive breast cancer (the comparative part following primary favorable safety and efficacy) | I/II (active, not recruiting) | NCT04983238 | |||||
| QuantumLeap Healthcare Collaborative | patients with breast cancer (I-SPY TRIAL; I-SPY will compare the efficacy of novel drugs in combination with standard chemotherapy with the efficacy of standard therapy alone) | II (recruiting) | NCT01042379 | |||||
| QuantumLeap Healthcare Collaborative | patients with certain HER-positive advanced solid tumors or HER2-low breast cancer and patients with HER2-positive or -low breast cancer | I/Ib (recruiting) | NCT04602117 | |||||
| Byondis | patients with locally advanced or metastatic solid tumors, including breast cancer | I (completed) | NCT02277717 | |||||
| Byondis | patients with locally advanced or metastatic HER2-expressing solid tumors of any origin (part 1) and patients with advanced or metastatic breast, ovarian or endometrial cancers (part 2) (SYD985 in combination with niraparib) | I (active, not recruiting) | NCT04235101 | |||||
| SBT6050 | anti-HER2 IgG | TLR8 agonist | – | – | Silverback Therapeutics | patients with advanced HER2-expressing solid tumors (as monotherapy or in combination with PD-1 inhibitors, including pembrolizumab or cemiplimab) | I/Ib (active, not recruiting) | NCT04460456 |
| Silverback Therapeutics | patients with pretreated unresectable locally advanced and/or metastatic HER2-expressing or HER2-amplified cancers, including HER2-positive breast cancer (SBT6050 in combination with other HER2-directed therapies, including T-DXd, tucatinib, trastuzumab, and capecitabine) | I/II (terminated) | NCT05091528 | |||||
| BDC-1001 | humanized IgG1 (trastuzumab biosimilar) | TLR7/TLR8 agonist | non-cleavable | – | Bolt Biotherapeutics | patients with advanced HER2-expressing solid tumors (as monotherapy or in combination with nivolumab) | I/II (recruiting) | NCT04278144 |
| MEDI4276 | humanized biparatopic antibody (trastuzumab & 39S) | AZ13599185 (a tubulysin derivative) | cleavable (peptide-based maleimidocaproyl) | 4.0 | MedImmune | patients with HER2-expressing breast or gastric cancers | I/II (completed) | NCT02576548 |
| RC48-ADC (disitamab vedotin; Aidixi) | humanized IgG1 (hertuzumab) | MMAE | cleavable (mc-val-cit-PABC) | 4.0 | RemeGen | patients with locally advanced or metastatic breast cancer with HER2-low expression | III (recruiting) | NCT04400695 |
| RemeGen | patients with HER2-positive metastatic breast cancer with or without liver metastases | II/III (recruiting) | NCT03500380 | |||||
| Cancer Institute and Hospital, Chinese Academy of Medical Sciences | patients with HER2-expression metastatic breast cancer with abnormal activation of the PAM (PI3K/Akt/mTOR) pathway | II (recruiting) | NCT05331326 | |||||
| Xijing Hospital | patients with HER2-positive breast cancer | II (not yet recruiting) | NCT05134519 | |||||
| Second Affiliated Hospital of Soochow University | patients with HER2-positive solid tumors (RC48-ADC in combination with hypofractionated radiotherapy, PD-1/PD-L1 inhibitor sequential GM-CSF and IL-2) | II (not yet recruiting) | NCT05115500 | |||||
| RemeGen | patients with advanced breast cancer with HER2-positive or -low expression | Ib (active, not recruiting) | NCT03052634 | |||||
| RemeGen | patients with advanced malignant solid tumors with HER2-positive | I (completed) | NCT02881138 | |||||
| RemeGen | patients with HER2-positive malignant in advanced malignant solid tumors | I (completed) | NCT02881190 | |||||
| Peking University | patients with HER2-positive advanced malignant solid tumors (JS001 in combination with RC48-ADC) | I (unknown) | NCT04280341 | |||||
| ARX788 | humanized mAb incorporated with pAF (a non-natural amino acid) | MMAF | non-cleavable (hydroxylamine-PEG4) | 1.9 | Caigang Liu | patients with HER2-positive breast cancer (ARX788 in combination with pyrotinib maleate versus TCBHP [trastuzumab plus pertuzumab with docetaxel and carboplatin]) | II/III (recruiting) | NCT05426486 |
| – | Metastatic breast cancer/gastric cancer | II/III | CTR20201708 | |||||
| Fudan University | patients with unresectable and/or metastatic breast cancer with HER2-low expression | II (recruiting) | NCT05018676 | |||||
| Fudan University | patients with HER2-positive, metastatic breast cancer whose disease is resistant or refractory to TKI | II (recruiting) | NCT05018702 | |||||
| Shengjing Hospital | patients with stage II-III HER2-positive breast cancer who have poor outcomes after treatment with trastuzumab and pertuzumab (pyrotinib maleate in combination with ARX788) | II (recruiting) | NCT04983121 | |||||
| Ambrx | patients with HER2-positive, metastatic breast cancer whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens | II (active, not recruiting) | NCT04829604 | |||||
| Ambrx | patients with HER2-mutated or HER2-amplified/overexpressed locally advanced or metastatic solid tumor cancers, including breast cancer, whose prior standard of care therapies have failed | II (withdrawn) | NCT05041972 | |||||
| Ambrx | patients with advanced cancer, including breast cancer, whose HER2 test results are ISH-positive or IHC 3+, based on safety, tolerability, PK findings, and antitumor activity | I (active, not recruiting) | NCT03255070 | |||||
| – | HER2-positive breast cancer | I | CTR20171162 | |||||
| – | HER2-positive gastric and breast cancer | I | CTR20190639 | |||||
| Zhejiang Medicine | patients with metastatic cancers with HER2 test result that is ISH-positive or IHC 3 + or 2+, including breast cancer | I (terminated) | NCT02512237 | |||||
| MRG002 | humanized IgG1 (sugar-modified trastuzumab) | MMAE | cleavable (valine-citrulline) | 3.8 | Shanghai Miracogen | patients with HER2-positive breast cancer with liver metastases | II (recruiting) | NCT05263869 |
| Shanghai Miracogen | patients with HER2-positive advanced solid tumors | I (recruiting) | NCT04941339 | |||||
| Shanghai Miracogen | patients with HER2-positive unresectable locally advanced or metastatic breast cancer | II (recruiting) | NCT04924699 | |||||
| Shanghai Miracogen | patients with HER2-low locally advanced or metastatic breast cancer | II (recruiting) | NCT04742153 | |||||
| Shanghai Miracogen | patients with HER2-expressed advanced malignant solid tumors (MRG002 in combination with HX008) | I/II (recruiting) | NCT05338957 | |||||
| – | patients with HER2-positive advanced solid tumors, including breast cancer | I | CTR20181778 | |||||
| DP303c | humanized IgG1 (DP001) | MMAE | cleavable (NH2-PEG3-val-cit) | 2.0 | CSPC ZhongQi Pharmaceutical Technology | patients with HER2-positive unresectable locally advanced, relapsed, or metastatic breast cancer | II (not yet recruiting) | NCT05334810 |
| CSPC ZhongQi Pharmaceutical Technology | patients with HER2-positive advanced solid tumors, including breast cancer | I (unknown) | NCT04146610 | |||||
| XMT-1522 (TAK-522) | human IgG1 (HT-19) | AF-HPA | a biodegradable hydrophilic polymer | 12.0 | Mersana Therapeutics | patients with advanced breast cancer and either a HER2 IHC score of at least 1 + using a validated IHC assay or with evidence of HER2 amplification (patients with HER2-positive [by IHC or amplification] gastric cancer or NSCLC may also be eligible for participation in dose escalation) | Ib (completed) | NCT02952729 |
| XMT-2056 | human IgG1 (HT-19) | STING agonist | – | – | Mersana Therapeutics | patients with advanced/recurrent HER2-expressing solid tumors, including HER2-positive and HER2-low breast cancer | I (recruiting) | NCT05514717 |
| PF-06804103 | humanized IgG1 | PF-06380101 (Aur0101; auristatin-0101) | cleavable (valine-citrulline) | 4.0 | Pfizer | patients with HER2-positive and -negative breast and gastric cancer (as monotherapy or in combination with letrozole and palbociclib) | I (completed) | NCT03284723 |
| DHES0815A (RG6148) | humanized IgG1 (hu7C2) | PBD-MA | cleavable (disulfide) | 2.0 | Genentech | patients with advanced and/or metastatic HER2-positive breast cancer for whom established treatment has proven ineffective or intolerable or is unavailable | I (completed) | NCT03451162 |
| Zanidatamab zovodotin (ZW49) | humanized, bispecific IgG1 (Zanidatamab or ZW25) | N-acyl sulfonamide auristatin | cleavable | – | Zymeworks | patients with locally advanced (unresectable) or metastatic HER2-expressing cancers, including breast cancer | I (recruiting) | NCT03821233 |
| MM-302 | scFv (F5) | liposomal doxorubicin | PEG-DSPE | – | Pamela Munster | patients with advanced HER2-positive cancer with new or progressive brain metastases (64Cu-MM-302 and unlabeled MM-302 in combination with trastuzumab) | early I (withdrawn) | NCT02735798 |
| Merrimack Pharmaceuticals | patients with advanced HER2-positive breast cancer (MM-302 with trastuzumab or trastuzumab plus cyclophosphamide) | I (unknown) | NCT01304797 | |||||
| Merrimack Pharmaceuticals | patients with locally advanced/metastatic HER2-positive breast cancer (MM-302 plus trastuzumab versus the CPC plus trastuzumab) | II/III (terminated) | NCT02213744 | |||||
| GQ1001 | Anti-HER2 mAb | DM1 | – | – | GeneQuantum Healthcare (Suzhou) | patients with HER2-positive advanced solid tumors, including HER2-positive breast cancer | I (recruiting) | NCT04450732 |
| B003 | humanized IgG | DM1 | non-cleavable (SMCC) | – | Shanghai Pharmaceuticals Holding | patients with HER2-positive recurrent or metastatic breast cancer | I (active, not recruiting) | NCT03953833 |
| BB-1701 | anti-HER2 IgG | – | – | – | Bliss Biopharmaceutical (Hangzhou) | patients with locally advanced/metastatic HER2-expressing solid tumors, including breast cancer | I (recruiting) | NCT04257110 |
| SHR-A1811 | anti-HER2 IgG | – | – | – | Jiangsu HengRui Medicine | patients with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and taxane (SHR-A1811 versus pyrotinib in combination with capecitabine) | III (recruiting) | NCT05424835 |
| Suzhou Suncadia Biopharmaceuticals | patients with HER2-expressing advanced solid tumors (SHR-A1811 in combination with fluzoparib) | Ib/II (enrolling by invitation) | NCT05349409 | |||||
| Jiangsu HengRui Medicine | patients with HER2-positive non-resectable or metastatic breast cancer (SHR-A1811 in combination with pyrrolidone or patrozumab or SHR-1316 or albumin paclitaxel) | Ib/II (not yet recruiting) | NCT05353361 | |||||
| Jiangsu HengRui Medicine | patients with HER2-expressing or mutated advanced malignant solid tumors | I (recruiting) | NCT04446260 | |||||
| BICON-02 | trastuzumab | – | – | – | Biointegrator | patients with HER2-positive metastatic breast cancer, previously treated with trastuzumab | I (terminated) | NCT03062007 |
| TAA013 | trastuzumab | DM1 | non-cleavable (SMCC) | – | – | patients with relapsed HER2-positive breast cancer | I | CTR20181642 |
| – | patients with locally advanced or metastatic HER2-positive breast cancer (TAA013 versus lapatinib in combination with capecitabine) | III | CTR20200806 | |||||
| UJVIRA (ZRC-3256)a | trastuzumab | DM1 | non-cleavable (SMCC) | 3.5 | Cadila Healthcare | patients with HER2-positive metastatic breast cancer | III | CTRI/2018/07/014881 |
| SHR-A1201a | trastuzumab | DM1 | non-cleavable (SMCC) | 3.5 | Jiangsu Hengrui Pharmaceuticals | patients with metastatic breast cancer | I | CTR20191558 |
| DX126-262 | humanized IgG1 (DX-CHO9) | Tub114 (a tubulysin derivative) | – | 3.5–3.8 | – | patients with HER2-positive advanced breast and/or gastric cancer | I | CTR20191224 |
| HS630 | humanized mAb | DM1 | – | – | Zhejiang Hisun Pharmaceutical/Beijing Mabworks Biotech | patients with HER2-positive advanced breast cancer | I | CTR20181755 |
HER2, human epidermal growth factor receptor 2; ADC, antibody-drug conjugate; NSCLC, non-small cell lung cancer; DAR, drug-to-antibody ratio; MMAF, monomethyl auristatin F; MMAE, monomethyl auristatin E; PBD, pyrrolobenzodiazepine; seco-DUBA, seco-duocarmycin-hydroxybenzamide-azaindole; TLR, Toll-like receptor; mc-val-cit-PABC, maleimidocaproyl-valyl-citrullinyl-p-aminobenzyloxycarbonyl; pAF, para-acetyl phenylalanine; PEG, polyethylene glycol; AF-HPA, auristatin F-hydroxypropylamide; PBD-MA, pyrrolo[2,1-c][1,4]benzodiazepine monoamide; scFv, single-chain fragment variable; PEG-DSPE, poly(ethylene glycol)-distearoylphosphatidylethanolamine; SMCC, succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate; CPC, chemotherapy of physician’s choice; TPC, treatment of physician’s choice; TKI, tyrosine kinase inhibitors; ISH, in situ hybridization; IHC, immunohistochemistry; PK, pharmacokinetics; STING, the stimulator of interferon genes protein; –, unknown, undisclosed, or unavailable.
a
ADCs are the biosimilar of T-DM1; the linker structure, the payload, and DAR are speculated from T-DM1.