# HER2 ADCs as standard for HER2-positive serous endometrial cancer

Source: https://onco.cc/ideas/idea-her2-adc-serous-endometrial/  
OnCo record `idea-her2-adc-serous-endometrial` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Serous endometrial cancers often overproduce HER2. Enhertu already works in them; testing HER2 in every p53-abnormal tumour and using the ADC earlier could change outcomes for the worst subtype.

## Summary

Serous endometrial carcinomas, which fall in the p53-abnormal molecular class, frequently amplify HER2, and this idea proposes testing HER2 in every p53-abnormal tumour and using trastuzumab deruxtecan earlier. T-DXd produced a high response rate in HER2 IHC 3+ endometrial cancer in DESTINY-PanTumor02, leading to tumour-agnostic approval, and trastuzumab with chemotherapy improved progression-free survival in a randomised phase 2 reported by Fader in 2018. The rationale is strong single-agent activity, a defined biomarker, and a subtype with the shortest survival that gains least from immunotherapy. The proposed test is a randomised phase 3 of first-line chemo-immunotherapy with or without T-DXd in HER2-positive p53abn disease, at an early clinical stage; NRG-GY026 tests trastuzumab.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- Hypothesis: Adding T-DXd (or trastuzumab) to first-line chemo-immunotherapy in HER2-positive p53abn endometrial cancer improves PFS and OS.
- Rationale: Strong single-agent activity, a defined biomarker, and a subtype with the highest mortality and least benefit from immunotherapy.
- Proposed test: Randomised phase 3 of chemo-IO ± T-DXd (or sequential T-DXd) in HER2 IHC 2+/3+ p53abn disease; NRG-GY026 tests trastuzumab/pertuzumab with chemotherapy.
- Maturity: early-clinical

## Sources

- ClinicalTrials.gov NCT04482309: DESTINY-PanTumor02: https://clinicaltrials.gov/study/NCT04482309

## Connected records

- cancers: [Endometrial cancer](https://onco.cc/cancers/endometrial/), [p53-abnormal endometrial cancer, including uterine serous carcinoma](https://onco.cc/cancers/endometrial-p53-abnormal/), [Uterine carcinosarcoma](https://onco.cc/cancers/uterine-carcinosarcoma/)
- targets: [HER2](https://onco.cc/targets/her2/), [TP53](https://onco.cc/targets/tp53/)
- drugs: [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- terms: [Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)](https://onco.cc/terms/endometrial-molecular-classes/)
- trials: [DESTINY-PanTumor02](https://onco.cc/trials/destiny-pantumor02/)
- key papers: [Yarden and Sliwkowski 2001: untangling the ErbB signalling network](https://onco.cc/key-papers/paper-yarden-sliwkowski-erbb-network-nrmcb-2001/)

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