KEYNOTE-966

NCT04003636 📎

Regimen

Experimental
Pembrolizumab 200 mg q3w + gemcitabine 1000 mg/m2 d1, d8 + cisplatin 25 mg/m2 d1, d8 q3w × up to 8 cycles, then pembrolizumab 400 mg q6w maintenance up to 35 cycles total
Control
Placebo + gemcitabine/cisplatin same schedule, then placebo maintenance

Population

Advanced BTC (unresectable/metastatic), 1L treatment-naive; ICC ~43%, ECC ~17%, GBC ~30%, ampullary ~10%; global enrollment including Asia, Europe, Americas; PD-L1 unselected; largest of the IO+GemCis phase 3 trials by sample size

Key finding

KEYNOTE-966 independently confirmed the class effect of IO + GemCis in advanced BTC, with a HR of 0.83 (p=0.0034). As with TOPAZ-1, the median OS gain is modest (1.8 months) but highly statistically significant in the largest BTC phase 3 trial to date (N=1069). The higher GBC enrollment (~30%) is notable; prior studies were ICC-enriched. A post-hoc analysis suggested GBC subtype may derive less benefit, though this was underpowered. PD-L1 CPS ≥10 did not predict enhanced benefit, consistent with TOPAZ-1 findings. KEYNOTE-966 independently drove pembrolizumab + GemCis approval.

Source: PMID 37075781

Timeline

    Guideline citations

    • NCCN BTC (p.20)