DESTINY-PANTUMOR02

NCT04482309 📎

Regimen

Experimental
T-DXd (trastuzumab deruxtecan) 5.4 mg/kg IV q21d — HER2-directed antibody-drug conjugate (ADC) with DXd topoisomerase I inhibitor payload and high drug-to-antibody ratio 8:1
Control
single-arm / no comparator

Population

HER2-expressing (IHC 3+ or IHC 2+) advanced solid tumors across 7 tumor cohorts; BTC cohort: n=41 of 267 total. BTC cohort included ICC (~70%), GBC (~20%), ECC (~10%). HER2 overexpression (not amplification) the entry criterion; IHC 3+ and IHC 2+ subgroups analyzed separately. All patients had ≥1 prior therapy.

Key finding

T-DXd demonstrated substantial activity in HER2-overexpressing BTC, with a strong IHC 3+ signal (ORR 56.3%) contrasting with a modest IHC 2+ signal (20.0%), establishing HER2 IHC score as a response predictor. T-DXd received FDA tumor-agnostic accelerated approval in April 2024 for HER2-overexpressing (IHC 3+) solid tumors after prior therapy — covering BTC. Interstitial lung disease (ILD)/pneumonitis occurred in 5.6% of BTC cohort (grade ≥3 in 1.9%), representing the key safety concern requiring monitoring. The ADC mechanism broadens HER2 targeting to patients with HER2 overexpression (not requiring amplification).

Source: PMID 37870536

Timeline

    Guideline citations

    • NCCN BTC (p.40)