Table 7 Current and upcoming clinical trials of bispecific antibodies in breast cancer
Trial name | Primary author | Year | Study design | Line of therapy | Setting | Mechanism of Action: immune-cell engager (ICE), T-cell engager (TCE), NK engager, dual tumor associated antigen (TAA) | TAA | # Patients | Drug regimen | Results |
|---|---|---|---|---|---|---|---|---|---|---|
Bispecific antibody | ||||||||||
NCT05035836 | Valero | 2023 | Phase II | Neoadjuvant | Stage I HER2 + breast cancer | dual TAA | HER2 x HER2 | 11 | Zanidatamab | pCR 36%; pCR/RCB1 64% |
NCT04224272 | Escrivá-de-Romani | 2023 | Phase II | Previously treated | Advanced HR + /HER2 + breast cancer | dual TAA | HER2 x HER2 | 34 | Zanidatamab + Fulvestrant + Palbociclib | DLT in one patient (neutropenia) cORR 34.5% (95% CI 17.9—54.3) mPFS 11.3 mo (CI 5.6—NE) |
NCT02892123 | Meric-Bernstam | 2022 | Phase I | Heavily pretreated | Advanced/Metastatic HER2 + solid tumors, including MBC | dual TAA | HER2 x HER2 | 279 | Zanidatamab + chemotherapy | DLT not reached; grade 3 + AE 3% of patients ORR 37% (95% CI 27.0–48.7) Part 3 ongoing |
NCT04276493 | Wang | 2023 | Phase Ib/II | Previously treated | Advanced HER2 + breast cancer | dual TAA | HER2 x HER2 | 37 | Zanidatamab + Docetaxel | ORR = 90.9% (95% CI 75.7–98.1) 67.6% with grade 3 + treatment-related AE |
NCT03619681 | Zhang | 2022 | Phase I | Heavily pretreated | HER2 + MBC | dual TAA | HER2 x HER2 | 63 | KN026 | ORR 28.1% PFS 6.8 mo (95% CI 4.2–8.3) CDK12 amplified subgroup ORR 50% vs 0% (p = 0.05), PFS 8.2 mo vs 2.7 mo (p = 0.04) |
NCT04881929 | Ma | 2023 | Phase II | Neoadjuvant | Stage II-III HER2 + breast cancer | dual TAA | HER2 x HER2 | 30 | KN026 + Docetaxel | pCR 56.7% (95% CI 37.43–74.53) ORR 90% (73.47–97.89) Grade 3 + AE 53.5% |
NCT04521179 | Liu | 2022 | Phase II | Previously treated | HER2 + breast cancer | dual TAA | HER2 x HER2 | 36 | KN026 + KN046 | ORR 50% (95% CI 28.2–71.8) DCR 81.8% (59.7–94.8) PFS 5.6 mo (2.5—NE) |
NCT02912949 | Schram | 2022 | Phase II | Heavily pretreated | HER2 + breast cancer expressing NRG1 mutation | dual TAA | HER2 x HER3 | 5 | Zenocutuzumab | Response in 2/4 evaluable patients |
NCT03321981 | Pistilli | 2020 | Phase II | Previously treated with CDK4/6i | HR + , HER2-low mBC | dual TAA | HER2 x HER3 | 48 | Zenocutuzumab + Endocrine Therapy | DCR 45% (90% CI 32–59); 2 patients with partial response |
NCT03321981 | Hamilton | 2020 | Phase II | Previously treated with anti-HER2 ADC | HER2 + MBC | dual TAA | HER2 x HER3 | 28 | Zenocutuzumab + Vinorelbine + Trastuzumab | DCR 77% (90% CI 60–89); 1 patient with complete response and 4 patients with partial response |
NCT01304784 | Richards | 2014 | Phase I | Previously treated | HER2 + MBC | dual TAA | HER2 x HER3 | 46 | Arm A: MM-111 + Cisplatin + Capecitabine + Trastuzumab Arm B: MM-111 + Lapatinib ± Trastuzumab Arm C: MM-111 + Paclitaxel + Trastuzumab Arm D: MM-111 + Lapatinib + Trastuzumab + Paclitaxel Arm E: MM-111 + Docetaxel + Trastuzumab | MTD not met |
NCT00911898 | Beeram | 2010 | Phase I | Heavily pretreated | HER2 + advanced breast cancer | dual TAA | HER2 x HER3 | 11 | MM-111 | No DLT |
NCT01097460 | Higgins | 2011 | Phase I/II | Heavily pretreated | HER2 + MBC | dual TAA | HER2 x HER3 | 16 | MM-111 + Herceptin | No results available |
NCT01569412 | Haense | 2016 | Phase I | Heavily pretreated | HER2 + MBC | TCE | HER2 x CD3 | 5 | Ertumaxomab | One partial response No dose-limiting toxicities |
NCT02829372 | Wermke | 2018 | Phase I | Heavily pretreated | HER2 Positive solid tumor | TCE | HER2 x CD3 | 19 | GBR 1302 | Grade 1–2 CRS common; two patients with DLT. One patient with breast cancer has ongoing response at 4 mo |
NCT00027807 | Lum | 2014 | Phase I | Heavily pretreated | MBC | TCE | BATs (HER2 x CD3) | 23 | HER2Bi + IL-2 + G-CSF | Best response: Stable disease or better: 54.5% HER2 3 + OS 57.4 mo HER2 0–2 + OS 27.4 mo |
NCT01022138 | Lum | 2021 | Phase II | Heavily pretreated | Metastatic HER2/HR+ and TNBC with stable disease | TCE | BATs (HER2 x CD3) | 32 | HER2Bi + IL-2 + G-CSF | Overall OS 13.1 mo (95% CI 8.6–17.4) HER2-/HR + OS 15.2 mo (CI 8.6–19.8) TNBC OS 12.3 mo (2.1–17.8) Significant increases in interferon-γ immunospots, Th1 cytokines, Th2 cytokines, and chemokines after treatment |
NCT02659631 | Harding | 2022 | Phase I | Heavily pretreated | Advanced Solid Tumors | TCE | CD3 x p-cadherin | 5 | PF-06671008 | Best response: stable disease |
Selected upcoming clinical trials | ||||||||||
NCT06435429 |  |  | Phase III | Pretreated | HER2 + MBC | dual TAA | HER2 Bispecific | 550 | Arm A: Chemotherapy + Zanidatamab Arm B: Chemotherapy + Trastuzumab | PFS |
NCT05027139 |  |  | Phase I/II | Pretreated | HER2 + solid tumors, including MBC | dual TAA | HER2 Bispecific + Anti-CD47 | 52 | Zanidatamab + Evorpacept (ALX148) | Safety ORR |
NCT03842085 |  |  | Phase I | Metastatic | HER2 + solid tumors, including HER2 + MBC and HER2 low MBC | dual TAA | HER2x HER2 | 34 | MS301 | DLT |
NCT03272334 |  |  | Phase I/II | Second line | MBC | dual TAA | HER2 Bispecific | 33 | HER2Bi + Pembrolizumab | MTD |
NCT04143711 |  |  | Phase I/II | Previously treated | Advanced HER2 + solid tumors, including breast | NK cell engager | trispecific NK cell engager | 378 | Arm A: DF1001-001 Arm B: DF1001-001 + nivolumab Arm C: DF1001-001 + nab paclitaxel Arm D: DF1001-001 + sacituzumab govitecan | DLT Safety ORR |