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Drug Trials Snapshots BRUKINSA

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 BRUKINSA Prescribing Information for complete information.

BRUKINSA (zanubrutinib)
BROO-kin-sah
BeiGene
Approval date: November 14, 2019


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

BRUKINSA 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.

How is this drug used?

BRUKINSA is a capsule. It may be taken as two capsules twice a day, or four capsules once a day.

What are the benefits of this drug?

In the trials, about 84 percent of patients had a complete or partial shrinkage of their tumors after treatment.

BRUKINSA 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.

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 2014 Lugano Classification for Non-Hodgkin’s lymphoma (NHL). The primary efficacy outcome was overall response rate (ORR) per Independent Review Committee assessment

Table 2. Efficacy Results in Patients with MCL by Independent Committee

 

 

Trial 1
(N=86)

Trial 2
(N=32)

                      ORR (95% CI)

84% (74, 91)

84% (67, 95)

CR

59%

22%*

PR

24%

63%

Median DoR in months (95% CI)

19.5 (16.6, NE)

18.5 (12.6, NE)

ORR: overall response rate, CR: complete response, PR: partial response, DoR: duration of response, CI: confidence interval, NE: not estimable
* fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans were not required for response assessment

BRUKINSA Prescribing Information

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

  • Sex: BRUKINSA worked similarly in men and women.
  • Race: Most of the patients were Asians. Differences in how well the drug worked among races could not be determined because of the small number of patients in other races.
  • Age: BRUKINSA 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. Race was not explored in Trial 1 because all patients were Asian. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.

Table 3. Subgroup Analysis of Overall Response Rate According to the Lugano Classification -Trial 1

Group

ORR, r/n, % (95% CI)

CR, r/n, % (95% CI)

N (%)

86 (100)

86 (100)

Sex

     Women

15/19, 79 (54, 94)

8/19, 42 (20, 67)

     Men

57/67, 85 (74, 93)

43/67, 64 (52, 76)

Age

     < 65

59/64, 92 (83, 97)

41/64, 64 (51, 76)

     ≥ 65

13/22, 59 (36, 79)

10/22, 45 (24, 68)

Table 4. Subgroup Analysis of Overall Response Rate According to the Lugano Classification -Trial 2

Group

ORR, r/n, % (95% CI)

CR, r/n, % (95% CI)

N (%)

32 (100)

32 (100)

Sex

     Women

10/10, 100 (69, 100)

3/10, 30 (7, 65)

     Men

17/22, 77 (55, 92)

4/22, 18 (5, 40)

Race

     White

23/25, 92 (74, 99)

7/25, 28 (12, 49)

     Black or African American

0/1

0/1

     Asian

1/3

0/3

     Other

3/3

0/3

Age

     < 65 years

5/8, 62 (24, 91)

2/8, 25 (3, 65)

     ≥ 65 years

22/24, 92 (73, 99)

5/24, 21 (7, 42)

Region

     Australia/New Zealand

19/20, 95 (75, 100)

3/20, 15 (3, 38)

     North America

8/10, 80 (44, 97)

4/10, 40 (12, 74)

     Asia

0/2

0/2

r – responders,
n – number of patients in a subgroup
CI – confidence interval

Adapted from FDA Review

What are the possible side effects?

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

The most common side effects of BRUKINSA are low blood cell counts, upper respiratory tract infections, rash, bruising, diarrhea and cough.

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

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

Table 4. Adverse Reactions (≥ 10%) in Patients Receiving BRUKINSA in Trials 1 and 2

Body System

Adverse Reaction

Percent of Patients (N=118)

All Grades
%

Grade 3 or Higher
%

Blood and lymphatic system disorders

Neutropenia and
Neutrophil count decreased

38

15

Thrombocytopenia and
Platelet count decreased

27

5

Leukopenia and White blood count decreased

25

5

Anemia and Hemoglobin decreased

14

8

Infections and infestations

Upper respiratory tract infection ¶

39

0

Pneumonia §

15

10^

Urinary tract infection

11

0.8

Skin and subcutaneous tissue disorders

Rash ‖

36

0

Bruising*

14

0

Gastrointestinal disorders

Diarrhea

23

0.8

Constipation

13

0

Vascular disorders

Hypertension

12

3.4

Hemorrhage †

11

3.4^

Musculoskeletal and connective tissue disorders

Musculoskeletal pain ‡

14

3.4

Metabolism and nutrition disorders

Hypokalemia

14

1.7

Respiratory, thoracic and mediastinal disorders

Cough

12

0

^ Includes fatal adverse reaction.
* Bruising includes all related terms containing bruise, bruising, contusion, ecchymosis
† Hemorrhage includes all related terms containing hemorrhage, hematoma
‡ Musculoskeletal pain includes musculoskeletal pain, musculoskeletal discomfort, myalgia, back pain, arthralgia, arthritis
§ Pneumonia includes pneumonia, pneumonia fungal, pneumonia cryptococcal, pneumonia streptococcal, atypical pneumonia, lung infection, lower respiratory tract infection, lower respiratory tract infection bacterial, lower respiratory tract infection viral
‖ Rash includes all related terms containing rash
¶ Upper respiratory tract infection includes upper respiratory tract infection, upper respiratory tract infection viral

Table 5. Selected Laboratory Abnormalities* (>20%) in Patients with MCL in Trials 1 and 2

Laboratory Parameter

Percent of Patients (N=118)

All Grades (%)

Grade 3 or 4 (%)

   Neutrophils decreased

45

20

   Platelets decreased

40

7

   Hemoglobin decreased

27

6

   Lymphocytosis †

41

16

Chemistry abnormalities

 

 

   Blood uric acid increased

29

2.6

   ALT increased

28

0.9

   Bilirubin increased

24

0.9

* Based on laboratory measurements.
† Asymptomatic lymphocytosis is a known effect of BTK inhibition. It should not be regarded as an adverse reaction, and these patients should continue taking BRUKINSA.

BRUKINSA 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 Asians. 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?

Tables below summarize adverse events that occurred during the clinical trials by sex and age subgroups. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.

Table 6. Subgroup Analyses of Adverse Events by Sex

 

Adverse Event

Safety Population (Trials 1 and 2)
N=118

Men
(N=89)
%

Women
(N=29)
%

Any TEAE

96%

100%

≥ Grade 3

46%

66%

SAE

30%

38%

 

Table 7. Subgroup Analyses of Adverse Events by Age

 

Adverse Event

Safety Population (Trials 1 and 2)
N=118

< 65years
N= 72
%

≥ 65y -≤ 75years
N = 32
%

> 75years
N = 14
%

Any TEAE

100%

94%

100%

≥ Grade 3

38%

44%

71%

SAE

25%

31%

64%

Adapted from FDA Review

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved BRUKINSA based on evidence from two clinical trials (Trial 1/ NCT03206970 and Trial 2/ NCT 02343120) that evaluated 118 patients with MCL who had received at least one prior therapy.

Trial 1 was conducted at 13 sites in China, and Trial 2 was conducted at 25 sites in the United States, United Kingdom, Australia, New Zealand, Italy, and South Korea.

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

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trial. In total, 29 women (25%) and 89 men (75%) participated in the clinical trial.

FDA Review

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

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the clinical trial. In total, 25 White (21%), 89 Asian (76%) and 4 Other (3%).

FDA Review

Table 1. Baseline Demographics by Race

 

Race

Number of Patients

              Percentage

White

25

21

Asian

89

76

Black or African American

1

Less than 1

Other

3

3

FDA Review

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

Figure 3. Baseline Demographics by Age

 Pie charts summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total, 72 (61%) were less than 65 years, and 46 (39%) of patients were 65 years and older.

FDA Review

The table below summarizes demographics of all patients evaluated in the clinical trials.

Table 8. Baseline Demographics of Patients Enrolled in the Clinical Trials

Demographic Characteristic

Trial 1
N=86

Trial 2
N=32

TOTAL
N=118

Sex, n (%)   

    Women

19 (22)

10 (31)

29 (25)

    Men

67 (78)

22 (69)

89 (75)

Race, n (%)

    White

 

25 (78)

25 (21)

    Asian

86 (100)

3 (9)

89 (76)

    Black or African American

 

1 (3)

1 (<1)

    Other

 

3 (9)

3 (3)

Age (years)  

     Median (Min, Max)  

60.5 (34, 75)

70.5 (42, 86)

62 (34,86)

Age Group, n (%)

    < 65 Years

64 (74)

8 (25)

72 (61)

    ≥ 65 Years

22 (26)

24 (75)

46 (39)

Geographic Region

 

 

 

   China

86 (100)

0

86 (73)

   Australia

0

14 (44)

14 (12)

   New Zealand

0

  6 (19)

6 (5)

   South Korea

0

2 (6)

2 (2)

   USA

0

10 (31)

10 (8))

Adapted from FDA Review

How were the trials designed?

There were two trials that evaluated the benefit and side effects of BRUKINSA.

Trial 1 enrolled patients with MCL who had received at least one prior therapy. All patients received two BRUKINSA capsules twice daily until disease progression or unacceptable side effects.

Trial 2 enrolled patients with B cell lymphoma including MCL patients who were previously treated with BRUKINSA. Patients received either two BRUKINSA capsules twice daily or three BRUKINSA capsules once a day until disease progression or unacceptable side effects.

The benefit of BRUKINSA was evaluated by measuring how many patients experienced complete or partial shrinkage of their tumors after treatment (overall response rate). In trial 1 patients underwent PET (positron emission tomography) imaging for tumor assessment, while in Trial 2, computed tomography or magnetic resonance imaging was used.

How were the trials designed?

The safety and efficacy of BRUKINSA were established in two trials.

Trial 1 was a Phase 2 open-label, multicenter, single-arm trial of patients with MCL who had received at least one prior therapy. BRUKINSA was given orally at a dose of 160 mg twice daily until disease progression or unacceptable toxicity.

Trial 2 was a Phase 1/2 open-label, dose-escalation, global, multicenter, single arm trial of B cell malignancies including 32 previously treated MCL patients treated with BRUKINSA. BRUKINSA was given orally at doses of 160 mg twice daily or 320 mg daily.

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.

LINK TO PRESCRIBING INFORMATION

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