The AMPLIFY trial is a phase III international study comparing acalabrutinib venetoclax with or without obinutuzumab to chemoimmunotherapy as a standard of care in previously untreated fit patients with chronic lymphocytic leukaemia. It’s designed as potentially a registration trial for the combination of the second-generation BTK inhibitor acalabrutinib with venetoclax which would be the first such regimen to become available.

What are the key results?

The primary endpoint was IRC-assessed progression free survival comparing acalabrutinib, venetoclax to chemoimmunotherapy. The study did meet this primary endpoint. The estimated 3-year progression free survival with AV was 76% compared to 66% for chemo. There was no planned comparison between the AV and the AV obinutuzumab arms but the first key secondary endpoint was the IRC-assessed progression free survival for the AVO regimen compared to chemoimmunotherapy and that was also met with an estimated 3-year progression free survival of 83% for AVO compared to 66% for chemoimmunotherapy. There was also evidence of improved or prolonged overall survival with AV compared to chemoimmunotherapy in the overall analysis.

What is the clinical significance of these results?

The AV regimen, in addition to being highly effective, was also very well tolerated. The serious adverse events were rare. The most common side effect was neutropenia but that was generally manageable and febrile neutropenia was rare. Cardiovascular events were also uncommon. It’s a 14-month regimen so it’s time-limited so there is less opportunity for cardiac events that we’ve seen with continuous administration.

The results are quite exciting because the AV regimen is something that we can give to most of our CLL patients pretty easily once it’s available. Then looking at the combination with obinutuzumab, that does add some toxicity, some more neutropenia and infections but it does also appear to deepen response and extend progression free survival. So that’s a good regimen for our fitter, younger patients for whom maximising progression free survival is important.

Of course, the overall, overarching benefit of the study is that it will hopefully lead to FDA, EMA and international approvals for acalabrutinib venetoclax with or without obinutuzumab as a front-line regimen for CLL patients. So it will become available as another option for our patients.