T-DXd + Pyrotinib Hits 100% PR in Phase Ib First-Line HER2-Positive mBC (TROPHY)

Trastuzumab deruxtecan (T-DXd), a HER2-directed topoisomerase-I ADC, was paired with the irreversible pan-HER TKI pyrotinib in the TROPHY phase Ib dose-finding study (NCT06245824). Five previously untreated metastatic HER2-positive patients (DFI >6 mo from adjuvant therapy) received T-DXd 5.4 mg/kg Q3W plus pyrotinib 400 mg (n = 2) or 320 mg (n = 3) daily. One grade 3 anorexia DLT at 400 mg set the RP2D at 320 mg. All patients experienced diarrhea, nausea, and vomiting, but grade ≥3 events were limited (diarrhea in 1/3 at 320 mg; anorexia/ALT ↑ in 1/2 at 400 mg); no grade 4/5 toxicities or ILD were observed. Among four RECIST-evaluable patients, all achieved partial responses (ORR = 100%), a numerical step above the 80% ORR seen with pertuzumab-trastuzumab-docetaxel and the 75% ORR reported for T-DXd monotherapy in first-line exploratory cohorts.

https://aacrjournals.org/clincancerres/article/31/12_Supplement/P5-05-09/753702/Abstract-P5-05-09-Trastuzumab-deruxtecan-combined