Ceralasertib Alone Shows Little Benefit for Relapsed/Refractory CLL

Patients with relapsed/refractory chronic lymphocytic leukemia (CLL) experienced limited clinical benefit with ceralasertib monotherapy, according to study results published in Therapeutic Advances in Hematology.

“Acalabrutinib in combination with ceralasertib was tolerable and demonstrated limited preliminary clinical activity in two patients with BTK inhibitor–naive CLL and del(11q),” researchers reported. “However, findings are inconclusive due to the small sample size, and it is possible that responses in the combination arm were due to acalabrutinib.”

The open-label, proof-of-concept study investigated ceralasertib with and without acalabrutinib in 11 patients with relapsed/refractory CLL. In arm A, 5 patients received ceralasertib monotherapy 160 mg twice daily (BID) continuously, and 3 received patients ceralasertib monotherapy 160 mg BID for 2 weeks on followed by 2 weeks off. In arm B, 2 patients received acalabrutinib 100 mg BID continuously, followed by combination treatment with ceralasertib 160 mg BID for 1 week on, then 3 weeks off. One patient in arm B received acalabrutinib only.

Median duration of exposure was 3.5 months for ceralasertib in arm A, 7.2 months for ceralasertib in arm B, and 15.9 months for acalabrutinib in arm B.

Regarding safety and pharmacokinetics, the study’s primary objectives, the most common grade 3 or higher treatment-emergent adverse events were anemia and thrombocytopenia in arm A. No grade 3 or higher treatment-emergent adverse events occurred in arm B, according to the study. Ceralasertib plasma concentrations were similar whether the medication was administered alone or with acalabrutinib.

No responses were observed in arm A at a median follow-up of 15.1 months. Median progression-free survival was 3.8 months, and overall survival was 16.9 months. In arm B, the overall response rate was 100% at a median follow-up of 17.2 months, the study found. Median progression-free and overall survival were not reached in arm B.

“Patients were heavily pretreated (median of three prior lines of therapies); almost all patients in arm A had been previously exposed to Bruton tyrosine kinase (BTK) inhibition, whereas no patients in arm B had received a prior BTK inhibitor,” researchers wrote. “This suggests that the responses observed in arm B may be due to acalabrutinib.”

Reference:
Jurczak W, Elmusharaf N, Fox CP, et al. Phase I/II results of ceralasertib as monotherapy or in combination with acalabrutinib in high-risk relapsed/refractory chronic lymphocytic leukemia. Ther Adv Hematol. 2023;14:20406207231173489. doi:10.1177/20406207231173489