Ceralasertib Shows Limited Efficacy in R/R CLL With 11q Deletions

Wojciech Jurczak, MD, PhD, discussed the results of the clinical trial investigation of ceralasertib with or without acalabrutinib in patients with high-risk relapsed/refractory chronic lymphocytic leukemia.

Wojciech Jurczak, MD, PhD, head of the department of oncology at Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, discussed the results of the clinical trial investigation of ceralasertib (AZD6738) with or without acalabrutinib (Calquence) in patients with high-risk relapsed/refractory chronic lymphocytic leukemia (R/R CLL).

The phase 1/2 study (NCT03328273) investigated the ATR inhibitor ceralasertib in patients with R/R CLL who had a 17p deletion, TP53 mutation, or 11q deletion. The study had 2 cohorts, 1 received ceralasertib monotherapy and the other, which only included patients with 11q deletions, received combination ceralasertib plus acalabrutinib.

However, the monotherapy arm was discontinued due to dose-limiting hematologic toxicities, and no patients in this arm appeared to benefit from ceralasertib. Some partial responses (PRs) were observed in the combination therapy arm. There were no complete responses (CRs) in either arm.

Jurczak says that although the study did not have positive results as a whole, ceralasertib may have a role in patients with 11q deletions based on the results of the combination cohort, though it would need to be explored further as the cohort was not large. The ATR inhibitor would likely not be a good option in the first 2 lines of therapy but could be used in patients with 11q deletions whose disease progresses on BTK (Bruton tyrosine kinase) or BCL-2 inhibitors, according to Jurczsk.

TRANSCRIPTION:

0:08 | Throughout this study, we could not achieve any CRs. The only PRs we observed were in arm B, where it was acalabrutinib plus ceralasertib with 11q deletion. All the other patients either progressed, or we could observe just stabilization of the process. Therefore, as a conclusion, ceralasertib as a monotherapy was not recommended, and a combination therapy was potentially effective in the patients with 11q deletion, although the study didn't recruit well enough to find enough patients make the results meaningful.

The mechanism of action is unique, and it could be further explored in patients with 11q deletion, although I would rather not recommend it in the first 2 lines of therapy. In those with 11q deletion failing a more dedicated therapy like BTK inhibitors including pirtobrutinib, or BCL-2 inhibitors, it could be a reasonable option, and it could be further investigated in this cohort.