U.S. flag An official website of the United States government
  1. Home
  2. Drugs
  3. Development & Approval Process | Drugs
  4. Drug Approvals and Databases
  5. Drug Trials Snapshots: Calquence
  1. Development & Approval Process | Drugs

Drug Trials Snapshots: Calquence

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to CALQUENCE Prescribing Information for complete information.

CALQUENCE (acalabrutinib)
KAL-kwens
AstraZeneca Pharmaceuticals LP
Approval date: October 31, 2017


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

CALQUENCE is used to treat adults with mantle cell lymphoma (MCL) who have received at least one prior treatment for their cancer.

MCL is a rare, rapidly progressing cancer that forms in the lymph system. MCL is one type of B-cell non-Hodgkin lymphoma.

CALQUENCE was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trials to confirm that the drug works well.

How is this drug used?

CALQUENCE is a capsule. One capsule is taken twice a day, approximately 12 hours apart.

What are the benefits of this drug?

In the trial, 81 percent of patients had a complete or partial shrinkage of their tumors after treatment (40 percent had complete shrinkage, and 41 percent had partial shrinkage).

More trials are ongoing to assess whether there is a clinical benefit.

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results based on the tumor response according to the Lugano Classification for Non-Hodgkin’s lymphoma (NHL). The primary efficacy outcome was overall response rate (ORR) per investigator assessment.

Table 2: Efficacy Results in Patients with MCL

 Investigator Assessed
N=124
Independent Review
Committee (IRC) Assessed
N=124
Overall Response Rate (ORR)*
    Overall Response Rate (%) [95% CI]81 [73, 87]80 [72, 87]
    Complete Response (CR) (%) [95% CI]40 [31, 49]40 [31, 49]
    Partial Response (PR) (%) [95% CI]41 [32, 50]40 [32, 50]
Duration of Response (DoR)
    Median DoR in months [range]NR [1+ to 20+]NR [0+ to 20+]

*Per 2014 Lugano Classification.
CI= Confidence Interval; NR=Not Reached; + indicates censored observations
CALQUENCE Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: CALQUENCE worked similarly in men and women.
  • Race: Most of the patients were White. Differences in how well the drug worked among races could not be determined because of the small number of patients in other races.
  • Age: CALQUENCE worked similarly in patients younger and older than 65 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The table below summarizes efficacy results by demographic subgroups. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.

Table 3. Subgroup analysis of overall response rate by investigator assessment according to the Lugano classification

Table summarizes efficacy results by subgroup

Adapted from Clinical Study Report

What are the possible side effects?

CALQUENCE may cause serious side effects including bleeding, infections, decreased blood cell counts, new cancers and heart rhythm problems.

The most common side effects of CALQUENCE are low blood cell counts, headache, diarrhea, tiredness, muscle aches and bruising.

What are the possible side effects (results of trials used to assess safety)?

The tables below summarize adverse reactions and hematologic abnormalities in the clinical trial.

Table 4. Non-Hematologic Adverse Reactions* in ≥ 5% (All Grades) of Patients with MCL

Body System
Adverse Reactions
CALQUENCE 100 mg twice daily
N=124
All Grades (%)Grade ≥ 3 (%)
Nervous system disorders
   Headache391.6
Gastrointestinal disorders
   Diarrhea313.2
   Nausea190.8
   Abdominal pain151.6
   Constipation15-
   Vomiting131.6
General Disorders
   Fatigue280.8
Musculoskeletal and connective tissue disorders
   Myalgia210.8
Skin & subcutaneous tissue disorders
   Bruising†21-
   Rash†180.8
Vascular disorders
   Hemorrhage/Hematoma†80.8
Respiratory, thoracic & mediastinal disorders
   Epistaxis6-

*Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
†Bruising: Includes all preferred terms (PTs) containing ‘bruise,’ ‘contusion,’ ‘petechiae,’ or ‘ecchymosis’
Rash: Includes all PTs containing ‘rash’
Hemorrhage/hematoma: Includes all PTs containing ‘hemorrhage’ or ‘hematoma’

Table 5. Hematologic Adverse Reactions Reported* in ≥ 20% of Patients with MCL in Trial LY-004

Hematologic
Adverse Reactions
CALQUENCE 100 mg twice daily
N=124
All Grades (%)Grade ≥ 3 (%)
Hemoglobin decreased4610
Platelets decreased4412
Neutrophils decreased3615

*Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03; based on laboratory measurements and adverse reactions.

CALQUENCE Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The occurrence of side effects was similar in men and women.
  • Race: Most of the patients were White. Differences in the occurrence of side effects among races could not be determined because of the small number of patients in other races.
  • Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table below summarizes the three most frequent adverse reactions that occurred during the clinical trials by sex, age and race subgroup. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.

Table 6. Subgroup Analyses of Adverse Reactions(AR)

Adverse
Reaction
SexRaceAge
Men
N=99
n (%)
Women
N=25
n (%)
Black or AA
N=3
n (%)
White
N=92
n (%)
Other
N=29
n (%)
<65>
N=44
n (%)
≥65 y
N=80
n (%)
Any AR96 (97)25 (100)3 (100)89 (97)29 (100)43 (98)78 (98)
Headache33 (33)14 (56)1 (33)39 (42)7 (24)24 (55)23 (29)
Diarrhea31 (31)7 (28)1(33)28 (30)9 (31)14 (31)24 (30)
Fatigue27 (27)7 (28)1(33)33 (36)0 (0)16 (36)18 (23)

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved CALQUENCE based on evidence from one clinical trial (NCT02213926) that enrolled 124 patients with MCL who had received at least one prior therapy.

The trial was conducted in United States, France, Poland, Great Britain, Australia, Belgium, Spain, Italy, and Netherlands.

Figure 1 summarizes how many men and women were in the clinical trial.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trial of the drug CALQUENCE . In total, 99 men (80%) and  25 women (20%) participated in the clinical trial.

FDA review

Figure 2 and Table 1 below summarize the percentage of patients by race in the clinical trial.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race in the clinical trial. In total, 92 White (74%), 3 Black or African American (3%), and 29 with not reported race (23%), participated in the clinical trial.

Data on race and/or ethnicity were not collected in some European countries because of local regulations.

FDA review

Table 1. Baseline Demographics by Race

Race

Number of Patients

              Percentage

White

92

74

Black or African American

3

3

Not reported*

29

23

* Data on race and/or ethnicity were not collected in some European countries because of local regulations.
FDA review

Figure 3 summarizes how many patients of certain age were enrolled in the clinical trial.

Figure 3. Baseline Demographics by Age

Pie charts summarizing how many individuals of certain age groups were in the clinical trial. In total, 44 patients  were younger than 65 years (35%), and  80 patients were  65 years and older (65 %).

FDA review

Who participated in the trials?

The table below summarizes demographics of all patients enrolled in the clinical trial.

Table 7. Baseline Demographics of Patients Enrolled in the Clinical Trial

 CALQUENCE
N = 124
Sex n (%)
        Men99 (79.8)
        Women25 (20.2)
Age (years)
        Mean67
        Median68
        Min, Max42, 90
Age Group n (%)
        < 65="">44 (35.5)
        ≥ 65 years80 (64.5)
        ≥ 75 years32 (25.8)
Race n (%)
        White92 (74)
        Black or African American3 (2.4)
        Not Reported*29 (23)
Ethnicityn (%)
        Hispanic or Latino4 (3)
        Not Hispanic or Latino90 (73)
        Unknown*30 (24)
TrialSiten (%)
        United States45 (36)
        Ex-US79 (64)

*Data on race and/or ethnicity were not collected in some European countries because of local regulations.
Adapted from FDA Review

How were the trials designed?

There was one trial that evaluated the benefit and side effects of CALQUENCE in patients with MCL who had received at least one prior therapy.

All patients received CALQUENCE capsule twice daily until disease progression or unacceptable side effects.

The benefit of CALQUENCE was evaluated by measuring how many patients experienced complete or partial shrinkage of their tumors after treatment (overall response rate).

How were the trials designed?

The safety and efficacy of CALQUENCE were established in one single arm, multicenter, open-label trial that enrolled adult patients with mantle cell lymphoma who had received at least one prior therapy.

Patients received CALQUENCE orally at 100 mg twice daily until disease progression or unacceptable toxicity. The median duration of treatment was 16.6 months (range, 0.1 to 26.6).

The efficacy was established based on overall response rate (ORR) assessed according to the Lugano Classification for Non-Hodgkin’s lymphoma (NHL). Response was measured by tumor reduction and tumor activity as measured by PET scan.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

Back to Drug Trials Snapshots