# Two-target antibody drugs to close the antigen escape route

Source: https://onco.cc/ideas/idea-bio1-dual-antigen-adc-escape/  
OnCo record `idea-bio1-dual-antigen-adc-escape` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

If a drug relies on one marker, the tumour can survive by dropping it. A drug that recognises two markers at once makes that escape harder.

## Summary

Bispecific ADCs binding two tumour antigens can retain binding and internalisation when one antigen is lost, and may improve selectivity where either antigen alone is present on normal tissue. Several bispecific ADCs are in clinical development. The proposal is to test the antigen-escape hypothesis explicitly by comparing a bispecific ADC with its monospecific parent and measuring antigen status at progression.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Patients treated with a bispecific ADC show a lower rate of antigen-loss-mediated resistance at progression than those treated with the matched monospecific ADC, with comparable toxicity.
- Rationale: Dual-antigen targeting reduced escape in CAR-T experience with CD19 and CD22; the mechanism of escape is the same, and ADC engineering can now support two binding arms.
- Proposed test: Randomised phase 2 with mandatory progression biopsies comparing a bispecific ADC with its parent, with antigen-loss rate as a co-primary endpoint alongside progression-free survival.
- Maturity: preclinical-evidence
- Actor: industry

## Sources

- Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137

## Connected records

- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Bispecific ADC](https://onco.cc/technologies/bispecific-adc/)
- drugs: [Izalontamab brengitecan](https://onco.cc/drugs/izalontamab-brengitecan/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/), [SystImmune / Sichuan Biokin](https://onco.cc/companies/systimmune/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)

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