Table 1.
Clinical development of antibody–drug conjugates for patients with metastatic TNBC.
| Drug | Target | Antibody | Linker-payload | DAR | Study phase | # of patients | Patient cohort | Treatment arms | ORR | PFS | ClinicalTrials.gov identifier |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sacituzumab govitecan (IMMU-132) | Trop-2 | RS7 | CL2A-SN-38 | 7.6 | I/II | 108 | Metastatic TNBC | IMMU-132 | 33.3 | 5.5 | NCT01631552 |
| III | 488 | Metastatic TNBC | IMMU-132 | NR | NR | NCT02574455 | |||||
| Eribulin/Cape/VNR/GEM | |||||||||||
| Ladiratuzumab vedotin (SGN-LIV1a) | LIV-1 | hLIV22 | vc-MMAE | 4 | I | 366 | Metastatic BC | SGN-LIV1A | 32* | 0.94* | NCT01969643 |
| Ib/II | 310 | Metastatic TNBC | SGN-LIV1A + atezo | NR | NR | NCT03424005 | |||||
| Cape | |||||||||||
| I/II | 97 | Metastatic TNBC | SGN-LIV1A + pembro | NR | NR | NCT03310957 | |||||
| II | NR | BC | SGN-LIV1A followed by AC | NR | NR | NCT01042379 | |||||
| Standard therapy | |||||||||||
| Trastuzumab deruxtecan (DS-8201a) | HER2 | Anti-HER2 IgG | Peptide linker with DXd | 8 | I | 278 | Advanced solid malignant tumors | DS-8201a | 43%** | NR | NCT02564900 |
| III | 540 | HER2-low BC | DS-8201a | NR | NR | NCT03734029 | |||||
| Cape/eribulin/GEM/PTX/nab-PTX | |||||||||||
| AVID100 | EGFR | MAB100 | Cleavable linker with DM1 | Undisclosed | Ia/IIA | 90 | TNBC, HNSCC, NSCLC | AVID100 | NR | NR | NCT03094169 |
| U3-1402 | HER3 | Patritumab | Tetra-peptide based linker with DXd | 8 | I/II | 180 | Metastatic BC | U3-1402 | 42.9*** | NR | NCT02980341 |
| CAB-ROR2-ADC (BA3021) | Ror2 | CAB | Undisclosed | Undisclosed | I/II | 120 | Solid tumor, NSCLC, TNBC, Soft tissue sarcoma | BA3021 | NR | NR | NCT03504488 |
| Anti-CA6-DM4 immunoconjugate (SAR566658) | CA6 | DS6 | SPDB-DM4 | 1 | I | 114 | Solid tumors | SAR566658 | 60****/35***** | NR | NCT01156870 |
| II | 23 | TNBC | SAR566658 | NR | NR | NCT02984683 |
AC, doxorubicin plus cyclophosphamide; AF-HPA, auristatin F-hydroxypropylamide; atezo, atezolizumab; BC, breast cancer; Cape, capecitabine; DAR, drug antibody ratio; DXd, extecan derivative; EGFR, epidermal growth factor receptor; GEM, gemcitabine; HER2, human epidermal growth factor receptor 2; HNSCC, head and neck squamous cell carcinoma; MMAE, monomethyl auristatin E; NSCLC, non-small cell lung cancer; q2w, every 2 weeks; ORR, objective response rate; pembro, pembrolizumab; PFS, progression-free survival; PTX, paclitaxel; TNBC, triple negative breast cancer; vc, valine-citrulline; VNR, vinorelbine.
The ORR is evaluated in TNBC dose escalation and expansion cohorts.
The ORR is evaluated in 23 patients including 6 patients with low HER2-expressing breast or gastric or gastro-esophageal carcinomas.
The ORR is evaluated in 34 patients with HER3-positive breast cancer.
The ORR is evaluated in patients with dosing of 190 and 90 mg/m2 on day 1 and day 8.
The ORR is evaluated in patients with dosing of 150 and 120 mg/m2 q2w.