Lavinia Woodward, Scientific Advisory and Solutioning Director at Rancho BioSciences, shared on LinkedIn:
“ADCs at ESMO 2026: What will define competitive advantage?
In OptiTROP-Lung06, ORR was 50.2% versus 47.3%. Median PFS was 15.0 versus 5.7 months. The gap between those two comparisons is one of the (many) important ADC lessons from ESMO – European Society for Medical Oncology 2026 . Response incidence alone can conceal differences in response depth, durability, and sustained disease control.
This raises a broader question: what evidence should we require to call an ADC truly differentiated?
Antigen diversity is increasing faster than payload diversity. Programmes pursue TROP2, HER3, B7-H3, B7-H4, CEACAM5, c-MET, and bispecific targets, while repeatedly converging on topoisomerase-I inhibitor payloads. This creates a portfolio risk that target-by-target analysis can miss. A pipeline can cover several antigens while retaining exposure to related resistance biology.
I think the field now needs a construct-level sequencing model, with each treatment characterised by the whole therapeutic system:
- Target and spatial expression pattern
- Antibody, linker, drug-to-antibody ratio, and payload mechanism
- Previous ADC exposure and duration of benefit
- Resistance state and CNS status
- Cumulative toxicity and remaining therapeutic window
This model changes how I interpret several themes emerging from ESMO.
Target expression is one input into patient selection. Heterogeneity, internalisation, payload delivery, and tumour sensitivity may be equally important.
Low discontinuation does not establish low treatment burden; dose reductions, interruptions, and relative dose intensity determine how much of the intended construct patients ultimately receive. Earlier-line use raises the evidence standard. When an ADC replaces chemotherapy or enters curative-intent treatment, mature survival, cumulative toxicity, patient-reported outcomes, and cost-effectiveness become central to the value case.
The practical implications differ across the ecosystem:
- For drug developers, in addition to previous target, sequencing trials should in the least, stratify by previous payload. Report predecessor-successor pairs in enough detail to investigate cross-resistance.
- For service providers, this increases demand for dynamic biomarker development, longitudinal multi-omic analysis, exposure-response modelling, and harmonised post-ADC datasets.
- For investors, apparent pipeline breadth should be stress-tested against payload concentration, dose deliverability, and efficacy after previous ADC exposure.
Which variable will prove most useful for selecting the next ADC: target biology, payload history, resistance state, or remaining therapeutic window?
I have summarised some key questions raised by data coming from ESMO 2026 in the infographic below.
How Diversified Are ADC Pipelines? Different targets, same payload class.
ESMO 2026 highlights growing ADC target diversity, yet many investigational programmes converge on topoisomerase-I (TOP1) inhibitor payloads.
Prospective Phase Il studies at ESMO Breast Cancer 2026 reported limited activity when TOP1-based ADCs were used after prior TOP1 ADC exposure, including a 3.7% response rate in SATEEN (n=27). The October SWITCH study (4RO) further examines ADC sequencing when targets change but payload classes are conserved.
Together, these findings raise a question: how much biological diversification does a different target provide when the cytotoxic mechanism is shared?
Strategic Implication: ADC portfolio assessment should consider payload mechanisms, potential cross-resistance, and sequencing alongside target and linker diversity.
Does Response Rate Tell Us Enough?
OptiTROP-Lung06 (Phase III): Sac-TMT + pembrolizumab achieved similar ORR to chemoimmunotherapy (50.2% vs 47.3%), but substantially longer median PFS (15.0 vs 5.7 months; HR 0.49).
Strategic Implication: ORR alone can obscure differences in response depth and durability. ADC differentiation requires more than tumour shrinkage alone.
Target Expression = Response?
CLDN18.2 trials reported at ESMO use expression-based eligibility thresholds, while BEHOLD-1 (B7-H4) demonstrates responses across expression levels, and TROP2 programmes show activity without high-expression selection.
Strategic Implication: Antigen expression alone likely insufficient. ADC biomarkers must incorporate target heterogeneity, internalisation, payload delivery, tumour sensitivity.
Low Discontinuation = Tolerability?
Despite only 2% treatment-related discontinuation, dose reductions occurred in 47%, and interruptions in 51%.
What If ADCs Replace Chemo?
OptiTROP-Lung06 improved median PFS from 5.7 to 15.0 months by replacing platinum chemotherapy with sac-TMT in first-line immunotherapy; VOLGA improved EFS and OS with a peri-operative ADC regimen, Both raise questions about cumulative toxicity and treatment burden, with additional considerations in curative-intent settings, such as VOLGA.
Strategic Implication: Earlier ADC use makes treatment duration, cumulative toxicity, mature survival, and cost-effectiveness central to demonstrating value.
Where Will the Next Competitive Advantage Come From?
Competitive advantage in ADC development will increasingly depend on identifying who benefits, how prior treatment affects response, and whether efficacy can be sustained at tolerable exposure. This demands resistance-informed trials, better predictive biomarkers, and earlier consideration of sequencing, dose optimisation, and patient outcomes.”
You can also read: ESMO 2026: 10 ADCs in Lung Cancer to Watch
