Suzhou-based Ascentage Pharma (HKG: 6855) unveiled preliminary data from the global Phase II clinical study for its APG-2575, alone or combined with Calquence (acalabrutinib) plus rituximab, in recurrent/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The results were released at the 64th American Society of Hematology (ASH) annual meeting this year.
Study Enrollment and Patient Demographics
As of December 5, 2022, 164 patients were enrolled in the study. There were 46 patients in the APG-2575 monotherapy group, 39 in the rituximab combination group, and 79 enrolled in the acalabrutinib combination group. In the total population, 16 patients (9.8%) were newly treated, and 19 patients (11.6%) had used BTKi previously. In the combined group (n=118), 25 patients had TP53 mutation and/or del (17p) and 34 patients had no IGHV mutation. Median treatment time: APG-2575 monotherapy group was 16.5 (1-36) cycles, 11 (0-21) cycles in rituximab combined group, and 11 (1-24) cycles in acalabrutinib combined group.
Efficacy Results
In the monotherapy group, the ORR of patients reached 67% (29/43), of which 67% (4/6) were patients who had previously received BTKi and were refractory or intolerant. In the acalabrutinib combination group, the ORR of patients reached 98.6% (72/73), including 98% (56/57) in the relapsed/refractory population, 100% (16/16) in the initial treatment population, and 88% (7/8) in the past BTKi refractory or intolerant patients. In the rituximab combination group, the ORR was 79% (27/34).
Safety Profile
Common adverse events (AEs) at any level included granulocytopenia, diarrhea, and infection. No dose-limiting toxicity (DLT) was observed. No drug interaction was found in the combination therapy group.
APG-2575 Development and Mechanism of Action
APG-2575 is under development to treat a variety of hematologic malignancies by selectively blocking Bcl-2 to restore the normal apoptosis process in cancer cells. The drug, China’s first homegrown Bcl-2 inhibitor to enter the clinics, is subject to multiple clinical studies in blood tumors.-Fineline Info & Tech
