BeiGene remains bold with sonrotoclax

Sonrotoclax, the BCL2 inhibitor BeiGene hopes will challenge AbbVie's similarly acting Venclexta, has entered its third phase 3 trial, in relapsed chronic lymphoblastic leukaemia. The new study, Celestial-RRCLL, was recently revealed on the clinicaltrials.gov registry. Like sonrotoclax's first phase 3, the Celestial trial in front-line CLL, Celestial-RRCLL is a head-to-head challenge: both studies include Venclexta as an active comparator. This is a notably bold approach, in comparison with the Chinese company Ascentage Pharma, which is also testing its BCL2 inhibitor, lisaftoclax, in pivotal first-line and relapsed CLL trials – neither of which includes a comparison against Venclexta. Celestial-RRCLL's primary endpoint tests PFS for sonrotoclax plus Gazyva versus Venclexta plus Rituxan, but an analogous regimen will also play a key part: the trial includes a second experimental cohort, sonrotoclax plus Rituxan, and secondary endpoints, including OS, involve the comparison of this versus Venclexta plus Rituxan, according to the clinicaltrials.gov entry. A third phase 3 trial, in which sonrotoclax is combined with Brukinsa and tested against Brukinsa alone in relapsed mantle-cell lymphoma (where Venclexta isn't approved), began in February.

Selected pivotal trials of BCL2 inhibitors

Note: a third BCL2 inhibitor, InnoCare's mesutoclax, is in a phase 2/3 study in 1st-line CLL, but this is uncontrolled and primarily tests safety. Source: OncologyPipeline.