OnCo
ideasIdea

HER2 ADCs as standard for HER2-positive serous endometrial cancer

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.

DESTINY-PanTumor02 showed ORR 84.6% in HER2 IHC 3+ endometrial cancer, leading to tumour-agnostic approval. HER2 amplification occurs in ~25-30% of serous carcinomas. Trastuzumab with chemotherapy already improved PFS in a randomised phase 2 (Fader 2018).

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.
What would test it
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

Connected

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cancers

1
Endometrial cancer

targets

2
HER2TP53

drugs

2
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedADC
Trastuzumab deruxtecan · Enhertu

terms

1
Endometrial cancer molecular classes (POLEmut, MMRd, p53abn, NSMP)

trials

1
DESTINY-PanTumor02