Targeted Treatment of Chronic Lymphocytic Leukemia: Clinical Utility of Acalabrutinib

Figures & data

Figure 1 Acalabrutinib structure and mechanism of action.

Table 1 Relevant Clinical Trials of Acalabrutinib for the Treatment of Patients with CLL

Trial	Study Design/Agents Number of Patients (on Acalabrutinib Arms)	Median Follow-Up	Results	AEs (% of Patients)
ACE-CL-001 Phase Ib/II NCT02029443	Multicenter, open-label and dose-escalation study of acalabrutinib 134 RR	41 months	ORR, 94% 45-month PFS, 62% Median PFS, not reached	Any grade Diarrhea (52%) Headache (51%) Hypertension (22%) Atrial Fibrillation (7%) Major Bleeding (5%) Grade ≥3 Neutropenia (14%) Pneumonia (11%) Hypertension (7%)
ACE-CL-001 Phase Ib/II NCT02029443	Multicenter, open-label and dose-escalation study of acalabrutinib 99 TN	53 months	ORR, 97% Median DOR, not reached	Grade ≥3 Infection (15%) Hypertension (11%) Bleeding events (3%) Atrial fibrillation (2%)
ACE-CL-001 Phase Ib/II NCT02029443	Multicenter, open-label and dose-escalation study of acalabrutinib (ibrutinib-Intolerant cohort) 33 RR	19 months	ORR, 76% 24-month PFS, 75% Median PFS, not reached	Any grade: Diarrhea (58%) Headache (39%) Cough (33%) Grade ≥3: Neutropenia (12%) Thrombocytopenia (9%)
ACE-CL-208 Phase II NCT02717611	Multicenter, open-label study of acalabrutinib in subjects who are intolerant of ibrutinib 60 RR	19 months	ORR, 77% 21-month PFS, 76% Median PFS, not reached	Any grade: Diarrhea (48%) Headache (40%) Contusion (35%) Dizziness (32%)
ACE-CL-003 Phase Ib/II NCT02296918	Study of acalabrutinib in combination with obinutuzumab 19 TN 26 RR	42 months	ORR TN, 95% ORR RR, 92% 36-month PFS TN, 94% 36-month PFS RR, 88% Median PFS, not reached (TN, RR)	Any grade: Headache (56%) Grade ≥3: Neutropenia (24%) Syncope (11%) Weight gain (9%) Hypertension (7%)
ASCEND ACE-CL-309 Phase III NCT02970318	Randomized, multicenter, open-label study of acalabrutinib vs investigator’s choice (idelalisib plus rituximab or bendamustine plus rituximab) 155 RR	22 months	ORR, 80% ORR + PRL, 92% 18-month PFS, 82% Median PFS, not reached	Any grade: Headache (22%) Diarrhea (21%) Neutropenia (20%) Grade ≥3: Neutropenia (17%) Anemia (12%)
ELEVATE-RR ACE-CL-006 Phase III NCT02477696	Randomized, multicenter, open-label, non-inferiority study of acalabrutinib vs ibrutinib 268 RR	41 months	ORR, 81% Median PFS, 38.4 months	Any grade: Diarrhea (35%) Headache (35%) Cough (29%) URI (27%) Pyrexia (23%) Hypertension (9%) Grade ≥3: Neutropenia (20%) Anemia (12%) Pneumonia (11%) Thrombocytopenia (10%) Atrial Fibrillation (5%)
ELEVATE-TN Phase III ACE-CL-007 NCT02475681	Randomized, multicenter, open-label study of obinutuzumab plus chlorambucil vs acalabrutinib plus obinutuzumab vs acalabrutinib monotherapy 179 TN (A+O) 179 TN (A)	29.8 months	ORR A+O, 94% ORR A, 86% 24-month PFS A+O, 93% 24-month PFS A, 87% Median PFS, not reached (A+O, A)	Any grade (A+O, A): Headache (40%, 37%) Diarrhea (39%, 35%) Neutropenia (32%, 11%) Fatigue (28%, 18%) Contusion (24%, 15%) Arthralgia (22%, 16%) Atrial Fibrillation (3%, 4%) Grade ≥3 (A+O, A): Neutropenia (30%, 10%) Thrombocytopenia (8%, 5%) Anemia (6%, 7%)

Abbreviations: AEs, adverse events; TN, treatment-naïve; RR, relapsed/refractory; ORR, overall response rate; PFS, progression-free survival; PRL, partial response with lymphocytosis; DOR, duration of response; A+O, acalabrutinib + obinutuzumab cohort; A, acalabrutinib monotherapy cohort.