Antibody–drug conjugates are no longer confined to late-line metastatic breast cancer. At ESMO Congress 2026, taking place October 23–27 in Madrid, ADCs will appear across HER2-positive, HER2-low, HR-positive/HER2-negative and triple-negative breast cancer, from neoadjuvant treatment to first-line metastatic therapy and the increasingly difficult question of what to use after a previous ADC.
The programme is notable not simply because many ADCs are being studied, but because they represent very different biological strategies: HER2-directed ADCs with alternative architectures, TROP2 ADCs carrying different topoisomerase-I payloads, an EGFR×HER3 bispecific ADC, a B7-H3 ADC, a Nectin-4 ADC and the established microtubule-payload ADC T-DM1.
Several presentations are phase III studies capable of directly affecting treatment algorithms; others are early-phase signals that may determine where the next generation of ADCs moves.
Here are 10 breast cancer ADCs to watch at ESMO 2026.
Trastuzumab Deruxtecan: From Metastatic Standard to Early-Disease Strategy
Target: HER2
ADC: Trastuzumab deruxtecan, T-DXd
Key ESMO presentations: TALENT – LBA23; PREDICT-HER – LBA17; DESTINY-Breast09 analysis – LBA49; DESTINY-Breast11 – 543RO; DESTINY-Breast05 – 539RO
No ADC has a broader breast cancer presence at ESMO 2026 than trastuzumab deruxtecan. The most conceptually important presentation may be TALENT, which reports final results of neoadjuvant T-DXd with or without anastrozole, or T-DXd sequenced with chemotherapy, in HR-positive/HER2-low early breast cancer. This moves the HER2-low concept from metastatic treatment into the curative-intent setting.
That is important because HER2-low was initially defined therapeutically by activity of T-DXd in advanced disease. TALENT now asks whether relatively low HER2 expression can also be exploited before surgery and whether an ADC could eventually reduce dependence on conventional neoadjuvant chemotherapy in selected patients. T-DXd will also feature prominently in HER2-positive disease.
DESTINY-Breast09 LBA49 focuses on patients with baseline brain metastases receiving T-DXd plus pertuzumab versus taxane-trastuzumab-pertuzumab, directly addressing whether the first-line ADC strategy can provide strong intracranial as well as extracranial control. DESTINY-Breast11 543RO evaluates MRI-defined responses during neoadjuvant treatment, while DESTINY-Breast05 539RO provides patient-reported outcomes comparing T-DXd with T-DM1 in high-risk HER2-positive early breast cancer.
ESMO 2026 therefore shows T-DXd being tested not as one drug in one line, but as an increasingly broad HER2-directed treatment platform across disease stages.
Read About All DESTINY Breast Trials on OncoDaily
Trastuzumab Rezetecan: Another HER2 ADC Challenges the HER2-Low Landscape
Target: HER2
ADC: Trastuzumab rezetecan, SHR-A1811
Study: HORIZON-Breast06
Abstract: LBA13
One of the most important phase III ADC presentations is HORIZON-Breast06, evaluating trastuzumab rezetecan in HER2-low advanced breast cancer. Trastuzumab rezetecan combines trastuzumab-mediated HER2 targeting with rezetecan, an exatecan-derived topoisomerase-I inhibitor payload.
The relevance of HORIZON-Breast06 extends beyond whether SHR-A1811 is active. T-DXd established HER2-low disease as a therapeutically actionable category. Every subsequent HER2-directed ADC must therefore answer a more demanding question: can its antibody, linker, payload and pharmacologic characteristics create clinically meaningful differentiation from T-DXd?
If HORIZON-Breast06 is positive, the HER2-low landscape could evolve from a single dominant ADC to a competitive HER2 ADC class, creating new sequencing questions almost immediately.
Read About Trastuzumab Rezetecan on OncoDaily
TQB2102: A Biparatopic HER2 ADC Enters Phase III
Target: HER2
ADC: TQB2102
Study: APEX-Breast01
Abstract: LBA27
TQB2102 represents another approach to HER2-directed ADC engineering. Rather than using a conventional single HER2-binding epitope, TQB2102 is a biparatopic HER2 ADC, designed to bind two HER2 epitopes and deliver a topoisomerase-I inhibitor payload.
At ESMO 2026, APEX-Breast01 LBA27 will report randomized phase III results comparing TQB2102 with chemotherapy in HER2-low recurrent or metastatic breast cancer. Earlier phase I evidence showed antitumor activity in both HER2-positive and HER2-low metastatic breast cancer, including preliminary responses among patients with brain metastases.
The phase III study will determine whether those early signals translate into a clinically meaningful advantage. Together with HORIZON-Breast06, APEX-Breast01 makes ESMO 2026 particularly important for determining whether HER2-low treatment will remain dominated by T-DXd or expand into a multi-ADC therapeutic class.
Izalontamab Brengitecan: Bispecific ADC Targeting Comes to HR-Positive Disease
Targets: EGFR × HER3
ADC: Izalontamab brengitecan, iza-bren / BL-B01D1
Study: PANKU-Breast01
Abstract: LBA50
Perhaps the most structurally distinctive breast ADC at the meeting is izalontamab brengitecan. Iza-bren is a bispecific ADC targeting EGFR and HER3, rather than HER2 or TROP2.
PANKU-Breast01 is a randomized phase III study in previously treated unresectable locally advanced or metastatic HR-positive/HER2-negative breast cancer. This setting is becoming increasingly important.
Patients may already have received endocrine therapy, CDK4/6 inhibition, PI3K/AKT-directed treatment, oral SERDs and potentially other ADCs before reaching later-line therapy.
A bispecific ADC could theoretically provide broader tumor recognition across a heterogeneous cancer population where one antigen alone may not remain uniformly expressed.
The larger question raised by iza-bren is therefore whether dual-antigen targeting can provide a meaningful clinical advantage over traditional single-target ADC architecture.
Read About Iza-Bren on OncoDaily
Sacituzumab Tirumotecan: Mature Survival Data in TNBC
Target: TROP2
ADC: Sacituzumab tirumotecan, sac-TMT / MK-2870 / SKB264
Study: OptiTROP-Breast01
Abstract: 4639RO
Sacituzumab tirumotecan is one of the most closely watched next-generation TROP2 ADCs. At ESMO 2026, OptiTROP-Breast01 will present its final overall survival analysis comparing sac-TMT with chemotherapy in previously treated locally recurrent or metastatic TNBC.
That endpoint matters. As breast oncology becomes increasingly saturated with ADCs, response rate or even PFS alone may no longer be sufficient to define the optimal treatment sequence. Mature OS evidence will become increasingly valuable when clinicians must choose between multiple ADCs directed toward overlapping populations.
Sac-TMT is also structurally different from other TROP2 ADCs, carrying a belotecan-derived topoisomerase-I inhibitor payload with a distinct linker platform.
If mature survival data remain compelling, sac-TMT could become an important competitor within the rapidly expanding TROP2 ADC class.
Datopotamab Deruxtecan: The Brain Metastasis Question in First-Line TNBC
Target: TROP2
ADC: Datopotamab deruxtecan, Dato-DXd
Study: TROPION-Breast02
Abstract: LBA96
Datopotamab deruxtecan has already established substantial evidence in breast cancer, but ESMO 2026 focuses on one of the most clinically challenging groups: patients with brain metastases.
LBA96 will present an exploratory analysis of patients with baseline brain metastases from TROPION-Breast02, which evaluated first-line Dato-DXd versus chemotherapy in locally recurrent inoperable or metastatic TNBC among patients not candidates for immunotherapy.
As ADCs move earlier, CNS efficacy is becoming a critical differentiator. For a first-line treatment to become broadly useful in metastatic breast cancer, extracranial activity may no longer be enough. Clinicians increasingly need evidence demonstrating whether the drug can control established intracranial disease and delay CNS progression.
That makes the ESMO analysis clinically important even though it is exploratory rather than a new randomized primary endpoint.
Read More About Dato-DXd on OncoDaily
Sacituzumab Govitecan: The Established TROP2 ADC Still Shapes First-Line TNBC
Target: TROP2
ADC: Sacituzumab govitecan, SG
Programme: ASCENT-04/KEYNOTE-D19 analyses
Sacituzumab govitecan remains an essential part of the ADC discussion because the TROP2 field is no longer confined to later-line treatment.
ASCENT-04/KEYNOTE-D19 established SG combined with pembrolizumab as an important first-line strategy for PD-L1-positive metastatic TNBC, and Merck’s ESMO 2026 breast cancer programme includes additional patient-reported outcome analyses from the study.
SG delivers SN-38, the active metabolite of irinotecan, through TROP2 targeting. That differs substantially from Dato-DXd and sac-TMT despite all three being classified as TROP2 ADCs. This distinction matters increasingly because future sequencing will need to consider not only antigen choice but also payload class, linker chemistry, toxicity and potential cross-resistance.
At ESMO 2026, SG therefore serves as both an established standard and an important comparator for the next generation of TROP2-directed therapies.
SYS6043: B7-H3 Expands Into Breast Cancer
Target: B7-H3
ADC: SYS6043
Abstract: 5RO
One of the more novel targets in the breast programme is B7-H3. SYS6043 will be presented in rapid oral abstract 5RO, reporting safety and efficacy in patients with advanced breast cancer.
B7-H3 has become a major ADC target across several solid tumors because it is frequently overexpressed on malignant cells while having more limited expression in many normal tissues. Earlier first-in-human development of SYS6043 included patients with breast, ovarian, lung, cervical and other cancers, supporting further disease-specific evaluation.
The key ESMO question is whether the breast cancer cohort shows sufficient activity and tolerability to justify larger subtype-specific studies. If so, B7-H3 could potentially give breast cancer another ADC target beyond the now familiar HER2 and TROP2 axes.
Bulumtatug Fuvedotin: Changing Both Target and Payload After a Topo-I ADC
Target: Nectin-4
ADC: Bulumtatug fuvedotin, BFv / 9MW2821
Abstract: 4640RO
Bulumtatug fuvedotin may be one of the most conceptually interesting ADC presentations at the congress. The phase II study specifically enrolls patients with locally advanced or metastatic TNBC who have already been treated with a topoisomerase-I inhibitor-based ADC.
BFv changes two important components of the ADC construct. It targets Nectin-4, rather than HER2 or TROP2, and carries MMAE, a microtubule-disrupting payload rather than another topoisomerase-I inhibitor. That design directly addresses one of the major emerging problems in breast cancer: cross-resistance after ADC exposure.
If resistance is primarily caused by loss of the surface antigen, switching target may be sufficient. But if resistance is related to the topoisomerase-I payload, moving from one Topo-I ADC to another may provide limited benefit.
BFv therefore tests a potentially more comprehensive escape strategy: switch both the antigen and the payload mechanism.
Trastuzumab Emtansine: An Older ADC Still Relevant in an ADC-Rich Era
Target: HER2
ADC: Trastuzumab emtansine, T-DM1
Key presentations: DESTINY-Breast05 – 539RO; BRIDGET – 1767RO
T-DM1 may no longer be the newest HER2 ADC, but it remains highly relevant to ESMO 2026 because it represents a fundamentally different ADC architecture from the topoisomerase-I platforms dominating current development.
T-DM1 carries the DM1 microtubule inhibitor through a non-cleavable linker, whereas T-DXd carries a membrane-permeable topoisomerase-I payload. At ESMO, T-DM1 appears as the comparator in DESTINY-Breast05 patient-reported outcomes, evaluating T-DXd versus T-DM1 in high-risk HER2-positive early breast cancer.
It is also incorporated into BRIDGET, abstract 1767RO, which evaluates adding tucatinib to trastuzumab/pertuzumab or T-DM1 after isolated intracranial progression in advanced HER2-positive breast cancer.
T-DM1’s continued presence is clinically useful because it reminds us that ADC sequencing is not necessarily synonymous with moving from one topoisomerase-I payload to another. A mature ADC landscape may ultimately require deliberate payload rotation, not simply increasingly potent versions of the same mechanism.
ESMO 2026 Is Really About ADC Sequencing
The most important breast ADC presentation may ultimately not belong to any single molecule.
SWITCH, abstract 4RO, is a prospective phase II platform study explicitly examining target switching with conserved-payload ADCs after prior ADC treatment. That question captures where breast cancer treatment is heading.
A patient may now move through T-DXd, sacituzumab govitecan, Dato-DXd, sac-TMT or another emerging ADC. Several of these drugs may use different antibodies but still depend on a topoisomerase-I payload. Resistance could occur at multiple levels: reduced antigen expression, impaired internalization, lysosomal processing, linker cleavage, drug efflux or alterations affecting payload sensitivity.
Simply changing HER2 to TROP2, or TROP2 to HER3, may therefore not necessarily overcome resistance if the tumor has become resistant to the cytotoxic mechanism itself. This is why presentations involving BFv, SWITCH and multiple next-generation HER2 ADCs could ultimately be just as important as headline response rates.
A Second Theme: HER2-Low Is Becoming Crowded
The HER2-low landscape at ESMO 2026 deserves particular attention. T-DXd is already established as the benchmark, yet both trastuzumab rezetecan and TQB2102 now enter phase III discussion.
Meanwhile, TALENT pushes T-DXd into HER2-low early disease. The result is a major change in how HER2 expression is being treated conceptually. Rather than asking simply whether a cancer is HER2-positive, clinicians increasingly have to consider:
HER2-positive, HER2-low, HER2-ultralow, previous HER2 ADC exposure, intracranial disease and the molecular architecture of the ADC itself. The competitive question is becoming less “Does HER2-low respond to an ADC?”
That has already been answered.
The next question is:
“Which HER2 ADC should be used, when, and what comes after it?”
TROP2 Is Becoming a Therapeutic Class of Its Own
A similar transition is happening with TROP2. ESMO 2026 includes sacituzumab govitecan, datopotamab deruxtecan and sacituzumab tirumotecan.
These drugs share a target but are not pharmacologically interchangeable. SG uses SN-38. Dato-DXd uses the DXd platform. Sac-TMT uses a different topoisomerase-I inhibitor and linker architecture.
As all three move earlier in disease, the field will increasingly need direct or indirect evidence addressing whether treatment with one TROP2 ADC affects subsequent sensitivity to another.
That question could become one of the defining sequencing problems in metastatic TNBC and HR-positive/HER2-negative disease.
OncoDaily Takeaway
ESMO 2026 shows that breast cancer has entered the second generation of the ADC era. The first generation established that ADCs can dramatically improve outcomes.
The next phase is more complicated. T-DXd is expanding into early HER2-low disease and CNS-focused first-line analyses. Trastuzumab rezetecan and TQB2102 could create genuine competition within HER2-low metastatic breast cancer.
Izalontamab brengitecan introduces dual EGFR×HER3 targeting into phase III HR-positive disease. Sacituzumab tirumotecan, datopotamab deruxtecan and sacituzumab govitecan are turning TROP2 into an ADC class rather than a single-drug target.
And SYS6043 and bulumtatug fuvedotin are broadening the field toward B7-H3 and Nectin-4, potentially providing alternatives after resistance to current Topo-I ADCs. The central breast cancer question at ESMO 2026 is therefore no longer:
“Do ADCs work?”
It is:
“Which target, which payload, which disease stage, and what ADC should come next?”
