ideasIdea
Dual-payload ADCs in first line to prevent resistance
Rather than waiting for resistance to one payload and then switching, give two mechanisms from day one, as HIV therapy does.
Combination chemotherapy beats sequential single agents in curable cancers because it prevents selection of resistant clones. Dual-payload ADCs make this possible without doubling antibody dose.
Confidence
15%–35%likelyOnCo editors (initial estimate), 2026-09-07 · Phase 1 assets only; first-line use is years away.
Hypothesis
A TOP1 + tubulin (or TOP1 + DNA-crosslinker) dual-payload TROP2 or HER2 ADC produces longer PFS in first-line metastatic breast cancer than a single-payload ADC at equivalent toxicity.
Rationale
Orthogonal resistance mechanisms; ACR335 and Sutro/Mersana programmes demonstrate manufacturability.
What would test it
Phase 1 dose-finding then randomised phase 2 vs single-payload ADC; monitor resistance biomarkers at progression.
Maturity
speculative