Study Design

Accelerated approval of CALQUENCE was based on ORR in the Phase 2 LY-004 study1

  • LY-004: Phase 2, open-label, single-arm, multicenter trial of CALQUENCE monotherapy in patients (≥18 years) with MCL who had received ≥1 prior therapy (N=124)1,2

  • Patients received CALQUENCE 100 mg BID until disease progression or unacceptable toxicity1

Initial data analysis

  • Based on efficacy and safety endpoints that occurred from March 12, 2015, through approximately 14 months after the last subject was enrolled3

  • Independent Review Committee (IRC) and investigator assessments were conducted on primary and secondary endpoints per Lugano Classification response criteria for non-Hodgkin lymphoma (NHL)1

24-Month Update Analysis from LY-004

  • Based on the cumulative efficacy and safety endpoints that occurred from March 12, 2015, until data cutoff on February 12, 2018 (24-month update)3

  • Investigator assessments were conducted on primary and secondary endpoints per Lugano Classification response criteria for NHL3

  • The IRC-endpoint analyses were not conducted in the long-term data update. IRC and investigator data were highly concordant in the initial data analysis: 91.1% for overall response rate (ORR) and 93.5% for complete response (CR)3

Primary endpoint: Overall response rate (ORR) per 2014 Lugano Classification response criteria for non-Hodgkin lymphoma (NHL)1

  • ORR is defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR)*2

Secondary endpoints: Duration of response (DoR), progression-free survival (PFS), overall survival (OS)2

  • Key inclusion criteria1,2

    • Relapsed or refractory disease, defined as achieving less than partial response with the most recent treatment

    • Confirmed mantle cell lymphoma with translocation t(11;14) (q13;q32), overexpressed cyclin D1, or both

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

  • Key exclusion criteria2

    • Prior treatment with a BTK inhibitor

    • Significant cardiovascular disease

    • Anticoagulation with warfarin or equivalent vitamin K antagonists

*CR (complete response) is defined as the disappearance of evidence of disease including extranodal disease (if present at baseline) and/or PET negativity based on FDG uptake less than or equal to the liver by PET-CT scan; PR (partial response) is defined as a reduction of measurable or metabolic disease and no new lesions, as defined by PET-CT scan. Efficacy endpoints were assessed by the investigator and by an Independent Review Committee.4 Significant cardiovascular disease included uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.2

CALQUENCE: Evaluated in a Broad Range of Patients With Relapsed/Refractory MCL

Baseline Patient Characteristics1,2,5

Chart showing baseline characteristics of patients who had received at least one prior therapy and took CALQUENCE as a monotherapy.Chart showing baseline characteristics of patients who had received at least one prior therapy and took CALQUENCE as a monotherapy.

MIPI=Mantle Cell Lymphoma International Prognostic Index. §Alone or as part of a combination regimen.

CHOP=cyclophosphamide/doxorubicin/vincristine/prednisone; hyper-CVAD=cyclophosphamide/vincristine/doxorubicin/dexamethasone.

CALQUENCE Patient Profiles

Review characteristics that may aid in identifying potential CALQUENCE patients through a series of interactive patient profiles.

 

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IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib) capsules

Serious and Opportunistic Infections

Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.

Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jiroveci pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly.

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients.

Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding.

Consider the benefit-risk of withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients with hematologic malignancies treated with CALQUENCE. Grade 4 neutropenia developed in 12% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted.

Second Primary Malignancies

Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was skin cancer, reported in 6% of patients. Monitor patients for skin cancers and advise protection from sun exposure.

Atrial Fibrillation and Flutter

Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (e.g., palpitations, dizziness, syncope, dyspnea) and manage as appropriate.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) of any grade in patients with MCL were anemia,* thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%). The most common Grade ≥ 3 non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea (3.2%).

*Treatment-emergent decreases (all grades) of hemoglobin (46%), platelets (44%), and neutrophils (36%) were based on laboratory measurements and adverse reactions.

Dosage reductions or discontinuations due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively.

Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration with a strong CYP3A inhibitor. If a strong CYP3A inhibitor will be used short-term, interrupt CALQUENCE.

Moderate CYP3A Inhibitors: When CALQUENCE is co-administered with a moderate CYP3A inhibitor, reduce CALQUENCE dose to 100 mg once daily.

Strong CYP3A Inducers: Avoid co-administration with a strong CYP3A inducer. If a strong CYP3A inducer cannot be avoided, increase the CALQUENCE dose to 200 mg approximately every 12 hours.

Gastric Acid Reducing Agents: If treatment with a gastric acid reducing agent is required, consider using an H2-receptor antagonist or an antacid. Take CALQUENCE 2 hours before taking an H2-receptor antagonist. Separate dosing with an antacid by at least 2 hours.

Avoid co-administration with proton pump inhibitors. Due to the long-lasting effect of proton pump inhibitors, separation of doses may not eliminate the interaction with CALQUENCE

SPECIFIC POPULATIONS

Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus.

Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for at least 1 week following the last dose of CALQUENCE.

It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for at least 2 weeks after the final dose.

Avoid administration of CALQUENCE in patients with severe hepatic impairment. Dose modifications are not required for patients with mild or moderate hepatic impairment.

INDICATION AND USAGE

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Please see complete Prescribing Information including Patient Information.

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Reference:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.

References:

  1. Dreyling M, Aurer I, Cortelazzo S, et al. Treatment for patients with relapsed/refractory mantle cell lymphoma: European-based recommendations. Leuk Lymphoma. 2018;59(8):1814-1828.
  2. Sandoval-Sus JD, Sotomayor EM, Shah BD. Mantle cell lymphoma: contemporary diagnostic and treatment perspectives in the age of personalized medicine. Hematol Oncol Stem Cell Ther. 2017;10(3):99-115.
  3. Shah BD, Martin P, Sotomayor EM. Mantle cell lymphoma: a clinically heterogeneous disease in need of tailored approaches. Cancer Control. 2012;19(3):227-235.
  4. Parrott M, Rule S, Kelleher M, Wilson J. A systemic review of treatments of relapsed/refractory mantle cell lymphoma. Clin Lymphoma Myeloma Leuk. 2018;18(1):13-25.
  5. Cohen JB, Zain JM, Kahl BS. Current approaches to mantle cell lymphoma: diagnosis, prognosis, and therapies. Am Soc Clin Oncol Educ Book. 2017;37:512-525.
  6. Cheah CY, Seymour JF, Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34:1256-1269.
  7. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  8. Dreyling M, Ferrero S; on behalf of European Mantle Cell Lymphoma Network. The role of targeted treatment in mantle cell lymphoma: is transplant dead or alive? Haematologica. 2016;101(2):104-114.
  9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed May 17, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.
  10. Pal Singh S, Dammeijer F, Hendriks RW. Role of Bruton’s tyrosine kinase in B cells and malignancies. Mol Cancer. 2018;17(1):57.
  11. Barf T, Covey T, Izumi R, et al. Acalabrutinib (ACP-196): A covalent bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile. J Pharmacol Exp Ther. 2017;363(2):240-252.
  12. Barf T, Kaptein A. Irreversible protein kinase inhibitors: balancing the benefits and risks. J Med Chem. 2012;55(14):6243-6262.
  13. Paweletz CP, Andersen JN, Pollock R, et al. Identification of direct target engagement biomarkers for kinase-targeted therapeutics. PLoS One. 2011;6(10):e26459.
  14. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.

Reference:

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed May 17, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  2. Hendriks RW, Yuvaraj S, Kil LP. Targeting Bruton’s tyrosine kinase in B cell malignancies. Nat Rev Cancer. 2014;14(4):219-232.
  3. Barf T, Covey T, Izumi R, et al. Acalabrutinib (ACP-196): A covalent Bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile. J Pharmacol Exp Ther. 2017;363(2):240-252.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  2. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  3. Data on File, REF-33702, AstraZeneca Pharmaceuticals LP.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  2. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  3. Data on File, REF-43179. AstraZeneca Pharmaceuticals LP.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  2. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  3. Data on File, REF-43179. AstraZeneca Pharmaceuticals LP.
  4. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano Classification. J Clin Oncol. 2014;32:3059-3068.
  5. Data on File, REF-18540. AstraZeneca Pharmaceuticals LP.

References:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  2. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  3. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano Classification. J Clin Oncol. 2014;32:3059-3068.
  4. Data on File, REF-43179. AstraZeneca Pharmaceuticals LP.

References:

  1. Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018;391(10121):659-667.
  2. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  3. Data on File, REF-43179, AstraZeneca Pharmaceuticals LP.

Reference:

  1. CALQUENCE [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.