TOPAZ-1

NCT03875235 📎

Regimen

Experimental
Durvalumab 1500 mg IV q3w + gemcitabine 1000 mg/m2 d1, d8 + cisplatin 25 mg/m2 d1, d8 q3w × up to 8 cycles, then durvalumab 1500 mg q4w maintenance until progression
Control
Placebo + gemcitabine/cisplatin same schedule, then placebo maintenance

Population

Advanced BTC (unresectable or metastatic), 1L treatment-naive; intrahepatic cholangiocarcinoma ~56%, extrahepatic cholangiocarcinoma ~20%, gallbladder cancer ~19%, ampullary carcinoma ~5%; global (Asia ~54%, Europe ~30%, Americas ~16%); all PD-L1 unselected

Key finding

TOPAZ-1 was the first phase 3 trial to show a statistically significant OS benefit from adding a PD-L1 inhibitor (durvalumab) to GemCis in advanced BTC. The primary OS HR of 0.80 is statistically significant but clinically modest — median OS improvement is only 1.3 months. However, the 24-month OS landmark (25% vs 10%) demonstrates a meaningful tail enrichment, suggesting durable benefit in a subset. The benefit was consistent regardless of PD-L1 expression status, arguing against biomarker stratification for treatment selection. TOPAZ-1 led to durvalumab + GemCis approval by regulatory agencies in multiple countries.

Source: PMID 38319896

Timeline

    Guideline citations

    • NCCN BTC (p.69)