# Trastuzumab duocarmazine

Source: https://onco.cc/drugs/trastuzumab-duocarmazine/  
OnCo record `trastuzumab-duocarmazine` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A HER2 ADC with a DNA-alkylating payload that beat chemotherapy in a phase 3 trial yet never reached the market, because eye and lung toxicity and a stronger rival arrived first.

## Summary

Byondis' duocarmycin-payload HER2 ADC improved PFS over physician's choice in pretreated HER2+ metastatic breast cancer (TULIP, 2021; PFS 7.0 vs 4.9 months) but with frequent ocular toxicity (~78%) and ILD. The FDA issued a complete response letter in 2023; the EMA application was withdrawn in 2024. Trastuzumab deruxtecan's DESTINY-Breast03 result made its niche disappear.

Lesson: statistical significance is not enough when a competitor redefines the standard; payload toxicity profile decides whether an ADC survives.

## Fields

- Kind: Treatment
- Status: withdrawn
- Last checked: 2026-09-06
- Tags: failure; lesson:toxicity
- Code: SYD985
- Modality: ADC
- Mechanism: Trastuzumab with seco-DUBA duocarmycin via cleavable Val-Cit linker; DNA alkylation.
- Payload: seco-DUBA (duocarmycin)
- Linker: Val-Cit cleavable

## Sources

- TULIP (Ann Oncol 2021 abstract): https://www.annalsofoncology.org/article/S0923-7534(21)04434-8/fulltext

## Connected records

- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [HER2](https://onco.cc/targets/her2/)
- drugs: [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- companies: [Byondis](https://onco.cc/companies/byondis/)
- trials: [I-SPY 2.2](https://onco.cc/trials/i-spy-2-2/), [SYD985 in Patients With HER2-expressing Recurrent, Advanced or Metastatic Endometrial Carcinoma](https://onco.cc/trials/nct04205630/), [SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer](https://onco.cc/trials/nct03262935/)
- bottlenecks: [Failures are hidden](https://onco.cc/bottlenecks/b-negative-results/)

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