ASSURE Trial to Investigate Acalabrutinib in Treatment-Naïve and R/R CLL

Globally, 135 cancer research sites are recruiting patients with untreated and relapsed or refractory chronic lymphocytic leukemia (CLL) to receive acalabrutinib (Calquence) treatment in the phase 3b ASSURE clinical trial (NCT04008706).¹

To conduct the global, multicenter, open-label, single-arm, phase 3b study, an estimated 560 patients will be enrolled and divided into 3 cohorts, which will include at least 300 patients with treatment-naïve CLL, about 200 patients with relapsed/refractory CLL, and 70 to 100 patients who were previously treated with a Bruton’s tyrosine kinase (BTK) inhibitor. The primary end point being explored in the study is the safety and tolerability of acalabrutinib determined by the number of patients with adverse events. The secondary end points of the study include objective response rate, duration of response, and progression-free survival.

Investigators of the study will investigate response using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria. Information gathered during physical examinations, recording of symptoms, radiologic evaluations, and hematologic evaluations will all be utilized to determine the ORR. Investigators will also conduct safety follow-up visits roughly 30 days from the last dose of acalabrutinib treatment during the study. Any patients who continue to derive benefit from treatment at the end of 48 cycles are permitted to continue on treatment with acalabrutinib.

Other end points of ASSURE that are not key outcomes include pharmacokinetics, overall survival, event-free survival, quality of life, and patient-reported outcomes.

To be eligible for the study, patients must be at least 18 years of age with a diagnosis of CLL, active disease as per IWCLL criteria, be eligible for 1 of the 3 cohorts, and have an ECOG performance status of 2 or lower. Females of childbearing age must consent to use contraception during the study. The presence or absence of deletion 17p, 13q del, 11q del, and trisomy of chromosome 12 along with the percentage of cells with the deletion, as well as with TP53 sequencing must be shown through fluorescence in situ hybridization in all patients 60 days prior to screening in the study.

Patients will be excluded from ASSURE if they have a primary malignancy other than CLL, history of confirmed progressive multifocal leukoencephalopathy, central nervous system involvement by CLL, and certain comorbidities that may interfere with study treatment.

Acalabrutinib will be given to patients at 100 mg in a capsule that patients can take orally, twice daily with 8 oz of water.

Acalabrutinib is an oral, highly selective BTK inhibitor, and its use in relapsed/refractory CLL and small lymphocytic leukemia in a prior phase 2 study (NCT02029443).²

In 134 patients who had a median age of 66 years (range, 42-85) and were treated with a median of 2 (range, 1-13) prior therapies, treatment with acalabrutinib 100 mg twice daily for a median of 41 months (range, 0.2-58) achieved an ORR of 94%. The median DOR was not reached in the study. Further, a survival estimate showed a PFS rate of 62% (95% CI, 51%-71%) at 45 months.

The most common AEs observed in the study were diarrhea in 52% and headache in 51%. Five percent or more of patients experienced grade 3 AEs of which the most common were neutropenia (14%), pneumonia (11%), hypertension (7%), anemia (7%), and diarrhea (5%). The majority of the study population was able to continue receiving acalabrutinib despite AEs, but 21% did discontinue due to progressive disease, and 11% discontinued due to AEs.

The phase 2 study results lead investigators to determine that further study of acalabrutinib in untreated and treated patients with CLL is warranted. This investigation will be carried out in ASSURE at United States sites in Arizona, California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Minnesota, Missouri, Nebraska, New York, Pennsylvania, South Carolina, Tennessee, and Texas. The trial is also recruiting in South America, Canada, Australia, Taiwan, and across Europe.¹

_References:

_{1. Acalabrutinib safety study in untreated and relapsed or refractory chronic lymphocytic leukemia patients (ASSURE). Clinicaltrials.gov. Accessed October 5, 2021.https://bit.ly/3iz7TMa}

_{2. Byrd JC, Weirda WG, Schuh A, et al. Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: updated phase 2 results. Blood. 2020; 9;135(15):1204-1213. doi: 10.1182/blood.2018884940}