Merck challenges Astra’s bile duct monopoly

Astrazeneca’s Imfinzi is the only anti-PD-(L)1 drug approved for biliary tract cancer, but it might not be alone for long. After this month’s Asco-GI conference saw Roche’s Tecentriq underwhelm here, today Merck & Co said Keytruda succeeded in the Keynote-966 study. The Merck trial is analogous to Astra’s registrational Topaz-1 study, combining Keytruda with chemo in first-line biliary tract cancer, and showing an effect on its primary endpoint, overall survival, that the company called “statistically significant and clinically meaningful”. The bar is low, as Imfinzi plus chemo added just over a month of median OS to chemo alone, cutting risk of death by 20%. Meanwhile, Roche’s approach, in the Imbrave-151 trial, was different, investigating Tecentriq with or without Avastin, and not having a chemo control arm. Adding Avastin to Tecentriq cut risk of progression by 24%, and risk of death by 26%, but neither effect hit statistical significance. Since this trial was uncontrolled the absolute benefit is of interest: six-month OS was 92% for the combo and 81% for Tecentriq alone, while in Topaz-1 it was around 75%. With hints of a benefit in a patient subset, biomarker studies are ongoing, Asco-GI heard.

Anti-PD-(L)1 drugs in 1st-line biliary tract cancer
Study Design mOS mPFS
Topaz-1^ Imfinzi + chemo, vs chemo 12.8mth vs 11.5mth (HR=0.80) 7.2mth vs 5.7mth (HR=0.75)
Imbrave-151* Tecentriq + Avastin, vs Tecentriq NR vs 11.4mth (HR=0.74) 8.3mth vs 7.9mth (HR=0.76)
Keynote-966 Keytruda + chemo, vs chemo "Stat sig & clinically meaningful" Not reported
Notes: NR=not reached; ^approved use; *ph2 study, other two are ph3. Source: prescribing info, Asco-GI & company presentation.

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