# ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs

Source: https://onco.cc/roadmaps/adc-generations/  
OnCo record `adc-generations` (Roadmap). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Twenty-five years of trying to make chemotherapy hit only cancer cells, from the unstable first ADC to today's third-generation blockbusters and the fourth generation now in trials.

## Summary

This roadmap traces antibody-drug conjugates from the first attempts with murine antibodies and the unstable first approved ADC, gemtuzumab ozogamicin, through the second generation that proved the class with brentuximab vedotin and T-DM1. The third generation brought TOP1 payloads and bystander killing with trastuzumab deruxtecan and sacituzumab govitecan, then moved into earlier lines, new targets and ADC plus PD-1 combinations. The emerging fourth generation arrives as bispecific ADCs led by izalontamab brengitecan, then dual-payload, degrader, immune-stimulating and masked ADCs, before a speculative era of imaging-guided therapy. Each generation fixed the previous one's weakness; the route is linked from TNBC, HR-positive and HER2-positive breast cancer, NSCLC and ovarian cancer.

## Fields

- Kind: Roadmap
- Last checked: 2026-09-04

## Sources

- ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer (New England Journal of Medicine 2021): https://doi.org/10.1056/NEJMoa2028485
- DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer (New England Journal of Medicine 2022): https://doi.org/10.1056/NEJMoa2115022

## Connected records

- roadmaps: [Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs](https://onco.cc/roadmaps/chemotherapy-roadmap/), [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/)
- technologies: [AI-driven drug & target discovery](https://onco.cc/technologies/ai-drug-design/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Bispecific ADC](https://onco.cc/technologies/bispecific-adc/), [Degrader-antibody conjugate (DAC)](https://onco.cc/technologies/degrader-antibody-conjugate/), [Dual-payload ADC](https://onco.cc/technologies/dual-payload-adc/), [Functional (ex vivo) drug testing](https://onco.cc/technologies/functional-drug-testing/), [HER2 PET](https://onco.cc/technologies/her2-pet/), [Immune-stimulating antibody conjugate (ISAC)](https://onco.cc/technologies/immune-stimulating-adc/), [Immuno-PET](https://onco.cc/technologies/immuno-pet/), [Masked / conditionally active ADC](https://onco.cc/technologies/masked-adc/), [Peptide-drug & small-molecule-drug conjugates](https://onco.cc/technologies/peptide-drug-conjugate/), [Radio-antibody & radio-ADC](https://onco.cc/technologies/radioimmunotherapy/), [Site-specific conjugation & linker chemistry](https://onco.cc/technologies/site-specific-conjugation/), [TROP2 PET](https://onco.cc/technologies/trop2-pet/)
- drugs: [AK146D1](https://onco.cc/drugs/ak146d1/), [Brentuximab vedotin](https://onco.cc/drugs/brentuximab-vedotin/), [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/), [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Gemtuzumab ozogamicin](https://onco.cc/drugs/gemtuzumab-ozogamicin/), [Izalontamab brengitecan](https://onco.cc/drugs/izalontamab-brengitecan/), [Mirvetuximab soravtansine](https://onco.cc/drugs/mirvetuximab-soravtansine/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/), [Telisotuzumab vedotin](https://onco.cc/drugs/telisotuzumab-vedotin/), [Tilatamig samrotecan](https://onco.cc/drugs/tilatamig-samrotecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Trastuzumab emtansine](https://onco.cc/drugs/trastuzumab-emtansine/)
- targets: [CD33](https://onco.cc/targets/cd33/)
- trials: [ASCENT-04 / KEYNOTE-D19](https://onco.cc/trials/ascent-04/), [BL-B01D1-307](https://onco.cc/trials/bl-b01d1-307/), [DESTINY-Breast03](https://onco.cc/trials/destiny-breast03/), [DESTINY-Breast04](https://onco.cc/trials/destiny-breast04/), [EV-302 / KEYNOTE-A39](https://onco.cc/trials/ev-302/)
- terms: [ADC sequencing](https://onco.cc/terms/adc-sequencing/)
- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- ideas: [A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer](https://onco.cc/ideas/idea-tnbc-adc-sequencing-trial/)

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JSON: https://onco.cc/api/v1/entities/adc-generations.json