ERIC 2024 | A study investigating sonrotoclax in R/R and treatment-naïve CLL

In this study, sonrotoclax has been given to 97 patients so far with CLL. In this combination, it’s part of an overarching study, the B2B11417101 clinical trial, which uses the sonrotoclax in combination with zanubrutinib or as monotherapy for other low-grade lymphoproliferative disorders as well as CLL. So this is just the cohort of relapsed refractory CLL. So the patients receive three months of zanubrutinib before starting a sonrotoclax ramp up. In this cohort there were numerous sub-cohorts of different dosing of sonrotoclax from 40 milligrams up to I think 640 milligrams. At follow-up, which I think data cut-off was around October last year, that was around 19 months, the median follow-up. We had good overall response rates, which improved with time. CR CRi response rates increased at 48 months compared to the 24-month cut-off as well. And MRD was also assessed which also deepened with time. Side effect profile wise was things you’d expect with these agents. Neutropenia, some COVID infection, contusions was common. There were no incidents of atrial fibrillation in the cohort. One patient had to come off study after developing cryptococcus but all other patients continued on. I think one patient in the lowest dose group came off study with progression. With the treatment naive cohort of CLR patients, again this was in the 101 BeiGene study using combinations on sonrotoclax and zanubrutinib, again with a three-month zanubrutinib lead in to reduce risk of TLS and then the ramp up in two dosing cohorts, 116 and 320. There were around, I think, 47 patients in the treatment naive cohort. They, again, had really good response rates, which deepened with time. Overall response was 100%, broken down into CR, CRi and PR. Undetectable MRD to MR4 also, deepened with time. It was 100% in the 320 cohort at 48 weeks, but again, this was just one patient. So, similar adverse effects with neutropenia, contusion, no atrial fibrillation and no other cardiac comorbidities or complications. So overall really promising. Sonrotoclax as a BCL2 inhibitor is more potent than venetoclax and with less off-target effects so hopefully it will be applicable to the patient population if it does get approved.