CALQUENCE Rx

Mantle Cell Lymphoma 

• The efficacy of Calquence was based upon Trial LY-004 titled “An Open-label, Phase 2 Study of ACP-196 in Subjects with Mantle Cell Lymphoma” (NCT02213926). Trial LY-004 enrolled a total of 124 patients with MCL who had received at least one prior therapy.
• At baseline, 93% of patients had an ECOG performance status of 0 or 1. The median time since diagnosis was 46.3 months and the median number of prior treatments was 2 (range 1-5), including 18% with prior stem cell transplant. The most common prior regimens were CHOP-based (52%) and ARA-C (34%). At baseline, 37% of patients had at least one tumor with a longest diameter ≥ 5 cm, 73% had extra nodal involvement including 51% with bone marrow involvement. 
• Calquence was administered orally at 100 mg approximately every 12 hours until disease progression or unacceptable toxicity. The median dose intensity was 98.5%. The major efficacy outcome of Trial LY004 was overall response rate and the median follow-up was 15.2 months.
• Results showed that patients treated with Calquence achieved an ORR of 81% (95% CI, 73-87) with 40% of those having complete response and 41% having partial response. The median time to best response was 1.9 months. 

Chronic Lymphocytic Leukemia 

• The efficacy of Calquence in patients with CLL was demonstrated in two randomized, controlled trials. The indication for acalabrutinib includes patients with SLL because it is the same disease.

Chronic Lymphocytic Leukemia: ELEVATE-TN trial

• The efficacy of Calquence was evaluated in the ELEVATE-TN trial, a randomized, multicenter, open-label, actively controlled, 3 arm trial of Calquence in combination with obinutuzumab, Calquence monotherapy, and obinutuzumab in combination with chlorambucil in 535 patients with previously untreated chronic lymphocytic leukemia (NCT02475681).
• Patients were randomly assigned in a 1:1:1 ratio into 3 arms to receive: 
  • Calquence plus obinutuzumab (Calquence+G): Calquence 100 mg was administered approximately every 12 hours starting on Cycle 1 Day 1 until disease progression or unacceptable toxicity. Obinutuzumab was administered starting on Cycle 2 Day 1 for a maximum of 6 treatment cycles. Obinutuzumab 1000 mg was administered on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of Cycle 2 followed by 1000 mg on Day 1 of Cycles 3 up to 7. Each cycle was 28 days.
  • Calquence monotherapy: Calquence 100 mg was administered approximately every 12 hours until disease progression or unacceptable toxicity.
  • Obinutuzumab plus chlorambucil (GClb): Obinutuzumab and chlorambucil were administered for a maximum of 6 treatment cycles. Obinutuzumab 1000 mg was administered intravenously on Days 1 and 2 (100 mg on Day 1 and 900 mg on Day 2), 8 and 15 of Cycle 1 followed by 1000 mg on Day 1 of Cycles 2 to 6. Chlorambucil 0.5 mg/kg was administered orally on Days 1 and 15 of Cycles 1 to 6. Each cycle was 28 days.
• Efficacy was based on progression-free survival (PFS) as assessed by an Independent Review Committee (IRC). The median duration of follow-up was 28.3 months (range: 0.0-40.8 months).
• Results showed that patients who received Calquence had a longer PFS compared with those who received obinutuzumab plus chlorambucil. In the Calquence combination arm, risk of disease progression or death was reduced by 90% (hazard ratio [HR] 0.10; 95% CI, 0.06-0.17, P <.0001) and in the monotherapy arm it was reduced by 80% (HR 0.20; 95% CI, 0.13-0.30, P <.0001). 
• With a median follow-up of 28.3 months, median overall survival was not reached in any arm, with fewer than 10% of patients experiencing an event.

Chronic Lymphocytic Leukemia: ASCEND Trial

• The efficacy of Calquence in patients with relapsed or refractory CLL was based upon a multicenter, randomized, open-label trial (ASCEND; NCT02970318). The trial enrolled 310 patients with relapsed or refractory CLL after at least 1 prior systemic therapy.
• Patients were randomly assigned in a 1:1 ratio to receive either: 
  • Calquence 100 mg approximately every 12 hours until disease progression or unacceptable toxicity, or
  • Investigator’s choice: Idelalisib plus a rituximab product (IR) or bendamustine plus a rituximab product (BR).
• In the Calquence arm, the median treatment duration was 15.7 months, with 94% of patients treated for at least 6 months and 86% of patients treated for at least 1 year. In the investigator’s choice arm, the median treatment duration was 8.4 months, with 59% of patients treated for at least 6 months and 37% treated for at least 1 year.
• Efficacy was based on PFS as assessed by an IRC, with a median follow-up of 16.1 months (range 0.03-22.4 months). In this trial, treatment with Calquence resulted in longer PFS compared with the other standard treatments (HR 0.31; 95% CI, 0.20-0.49; P <.0001). There was no statistically significant difference in overall response rates between the two treatment arms.
• With a median follow up of 16.1 months, median overall survival was not reached in either arm, with fewer than 11% of patients experiencing an event.