Novel BCL2 Inhibitor Induces Responses in Patients with Relapsed/Refractory Disease

By Leah Sherwood - Last Updated: February 1, 2023

Data presented at the 2022 European Hematology Association (EHA) Congress showed that the BCL2 selective inhibitor lisaftoclax induced responses in patients with a variety of relapsed/refractory malignancies, including non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL).

Lisaftoclax is a novel, orally administered small-molecule BCL2 selective inhibitor that works by selectively blocking the antiapoptotic protein BCL2 and restoring the normal apoptosis process in cancer cells.

In the study, lisaftoclax was well tolerated at doses of up to 800 mg/day, with no evidence of tumor lysis syndrome (TLS). In addition, lisaftoclax induced four complete responses (CRs) and eight partial responses (PRs) in 32 evaluable patients, resulting in an overall response rate (ORR) of 37.5%.

The phase I study targeted a range of relapsed/refractory hematologic malignancies, including CLL/small lymphocytic lymphoma, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and T-cell NHL.

Patients were dosed with lisaftoclax orally once daily in 28-day cycles at a dose range of 20 mg to 800 mg. A daily ramp-up schedule was used in patients with CLL or NHL with medium to high risk of TLS. The median treatment duration was four cycles.

In the 11 evaluable patients with CLL, the ORR was 63.6%, the CR rate was 27.3%, and the PR rate was 36.4%. In patients with CLL treated at doses of 200 mg and higher, the ORR was 87.5%. In the six evaluable patients with MCL, one patient achieved CR and one achieved PR. In the four evaluable patients with MZL, two achieved PR. In the three evaluable patients with T-cell NHL, one achieved PR.

“[Lisaftoclax] has shown favorable tolerability and efficacy in multiple clinical studies in patients with solid tumors and hematologic malignancies,” said Yifan Zhai, MD, PhD, Chief Medical Officer of Ascentage Pharma, manufacturer of lisaftoclax, in a statement.

Source: Ascentage Pharma Press Release, June 2022

Post Tags:BCL2 InhibitorEHA 2022Non-Hodgkin Lymphoma
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