ASH 2021 | Efficacy and safety of BGB-11417 in B-cell malignancies
Chan Yoon Cheah, MBBS, Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, Australia, presents updates from the open label, multicenter, Phase I BGB-11417-101 trial (NCT04277637) of BGB-11417, a BCL2 inhibitor, in patients with various B-cell malignancies. Patients either received BGB-11417 as a monotherapy or with zanubrutinib. A favorable efficacy and safety profile was reported in patients receiving BGB-11417 monotherapy, although there were fewer responses were reported in patients with non-Hodgkin subtypes. Dr Cheah also discusses future directions in the trial, including expansion to additional subtypes. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
BGB-11417 is an oral selective BCL-2 inhibitor. So it’s a similar class of drug to Venetoclax. So it has a similar mechanism of action. The difference between BGB-11417 and Venetoclax is that the molar-for-molar potency is substantially higher for 11417, about tenfold over Venetoclax. And we are certainly expecting that the efficacy will be in line with that. So in this poster, we are performing in an ongoing Phase I dose escalation study of this agent...
BGB-11417 is an oral selective BCL-2 inhibitor. So it’s a similar class of drug to Venetoclax. So it has a similar mechanism of action. The difference between BGB-11417 and Venetoclax is that the molar-for-molar potency is substantially higher for 11417, about tenfold over Venetoclax. And we are certainly expecting that the efficacy will be in line with that. So in this poster, we are performing in an ongoing Phase I dose escalation study of this agent. Both as monotherapy and in combination with zanubrutinib, which is BeiGene’s BTK inhibitor, an oral covalent BTK inhibitor. There are dosing cohorts in the common B-cell malignancies, including non-Hodgkin lymphoma, chronic lymphocytic leukemia. And we’ve recently opened cohorts of Waldenstrom Macroglobulinemia and mantle cell lymphoma. And for CLL, at least at this point, we’re doing combinations with both 11417 and zanubrutinib.
So these data again were presented at EHA. And at that stage, we had encouraging safety profile with not a great deal of toxicity seen. And the drug seems to be pretty nice to use, and it is certainly effective in patients with CLL. We have fewer responses among the non-Hodgkin lymphoma subtypes, but most of the patients with NHL treated on the study have had diffuse large B-cell lymphoma. And we’ve had some patients with stable disease pushing out to a year or so, but no… And a few patients deriving benefit in terms of reduction in their tumor burden, but few objective responses. But in the Venetoclax experience, the objective response rate in DLBCL was relatively low anyway, about 18%. So we’re not expecting to see a huge amount of activity. I think the more interesting thing about this drug is it is looking very nice in combination with zanubrutinib. And that cohort in patients with previously treatment naive CLL has just opened up and we are pretty excited about that.
We are also as I mentioned, planning to test the combination in a number of other B-cell malignancy subtypes. So, always good to see emerging data for a new BCL-2 inhibitor. Last point to make on this is that tumor lysis syndrome is a class specific toxicity of BCL-2 inhibitors, which we have not seen using the dose escalation strategy employed so far. I think maybe one patient had laboratory TLS, but no clinical TLS. And we are moving to outpatient management for these patients as the study progresses, which is clearly a very good logistics thing for doctors and for patients that hospitalizations not required to get these patients with high tumor burden onto the drug.
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