Drugs

Drug Trials Snapshots: EMPLICITI

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 the EMPLICITI Prescribing Information for complete information.

EMPLICITI (elotuzumab)
(em-plis-city)
Bristol-Myers Squibb
Approval date: November 30, 2015


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

EMPLICITI is a drug used for the treatment of a form of blood cancer called multiple myeloma. It is for use in patients who have received one to three prior medications and is intended to be used in combination with another FDA-approved treatment for multiple myeloma called Revlimid (lenalidomide) and dexamethasone (a type of corticosteroid).

How is this drug used?

EMPLICITI is given by a healthcare provider as an infusion into a vein. It is given according to a specific schedule.

What are the benefits of this drug?

Those taking EMPLICITI plus Revlimid and dexamethasone experienced a delay in the amount of time (19.4 months) before their cancer worsened (called progression-free survival) compared to patients taking only Revlimid and dexamethasone (14.9 months).

Also, 78.5% of patients taking EMPLICITI with Revlimid and dexamethasone saw a complete or partial shrinkage of their tumors compared to 65.5% in those only taking Revlimid and dexamethasone.

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

The table and figure below summarizes efficacy results for the clinical trial.

Table 2. Efficacy Results

 EMPLICITI+
Lenalidomide/
Dexamethasone
N=321
Lenalidomide/
Dexamethasone

N=325
PFS
Hazard Ratio [95% CI]0.70 [0.57, 0.85]
Stratified log-rank test p-value*0.0004
Median PFS in months [95% CI]19.4 [16.6, 22.2]14.9 [12.1, 17.2]
Response
Overall Response (ORR) n (%)
[95% CI]
252 (78.5)
[73.6, 82.9]
213 (65.5)
[60.1, 70.7]
      p-value0.0002
     Complete Response (CR + sCR)†,§ n (%)14 (4.4)24 (7.4)
     Very Good Partial Response (VGPR) n (%)91 (28.3)67 (20.6)
     Partial Response (PR) n (%)147 (45.8)122 (37.5)

* p-value based on the log-rank test stratified by ß2 microglobulins (<3.5 mg/L vs 3.5 mg/L), number of prior lines of therapy (1 vs 2 or 3), and prior immunomodulatory therapy (no vs prior thalidomide only vs other).
European Group for Blood and Marrow Transplantation (EBMT) criteria.
p-value based on the Cochran-Mantel-Haenszel chi-square test stratified by ß2 microglobulins (<3.5 mg/L vs 3.5 mg/L), number of prior lines of therapy (1 vs 2 or 3), and prior immunomodulatory therapy (no vs prior thalidomide only vs other).
§ Complete response (CR) + stringent complete response (sCR).
EMPLICITI’s interference with the assessment of myeloma protein with immunofixation and serum protein electrophoresis assay may interfere with correct response classification [see Drug Interactions (7)].

EMPLICITI Prescribing Information, Table 7

Figure 5. Progression-Free Survival

Figure summarizes percentage for probability progression-free and months of progression-free survival

EMPLICITI Prescribing Information, Figure 1

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

Subgroup analyses were conducted for sex, race and age.

  • Sex: EMPLICITI worked similarly in men and women.
  • Race: The majority of patients were white. Differences in response to EMPLICITI among races could not be determined.
  • Age: EMPLICITI worked similarly in patients below and above 65 years of age.

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

The figure below summarizes subgroup analysis for the primary endpoint, progression-free survival (PFS).

Figure 4. IRC-PFS Subgroup Hazard Ratios for the Randomized Clinical Trial

 Table summarizes subgroup analysis for the primary endpoint, progression-free survival (PFS)

RC=independent review committee
Clinical Trial Data

What are the possible side effects?

The most common side effects of Empliciti are fatigue, diarrhea, fever (pyrexia), constipation, cough, nerve damage resulting in weakness or numbness in the hands and feet (peripheral neuropathy), infection of the nose and throat (nasopharyngitis), upper respiratory tract infection, decreased appetite and pneumonia.

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

The table below summarizes adverse reactions occurring at a frequency of 10% or higher in the EMPLICITI arm and 5% or higher than the lenalidomide and dexamethasone arm for the randomized trial.

Table 3. Adverse Reactions with a 10% or Higher Incidence for EMPLICITI-Treated Patients and a 5% or Higher Incidence than Lenalidomide and Dexamethasone-Treated Patients [All Grades]

 EMPLICITI+
Lenalidomide and Dexamethasone
N=318
Lenalidomide and Dexamethasone

N=317
Primary TermAll GradesGrade 3/4All GradesGrade 3/4
Fatigue*61.612.651.711.7
Diarrhea46.95.036.04.1
Pyrexia37.42.524.62.8
Constipation35.51.327.10.3
Cough34.30.318.90
Peripheral Neuropathy26.73.820.82.2
Nasopharyngitis24.5019.20
Upper Respiratory Tract Infection22.60.617.41.3
Decreased Appetite20.81.612.61.3
Pneumonia§20.114.214.29.5
Pain in Extremities16.40.910.10.3
Headache15.40.37.60.3
Vomiting14.50.38.80.9
Weight Decreased13.81.36.00
Lymphopenia13.28.86.93.2
Cataracts11.96.36.32.8
Oropharyngeal Pain10.104.40

* The term fatigue is a grouping of the following terms: fatigue and asthenia.
The term cough is a grouping of the following terms: cough, productive cough, and upper airway cough.
The term peripheral neuropathy is a grouping of the following terms: peripheral neuropathy, axonal neuropathy, peripheral motor neuropathy, peripheral sensory neuropathy, and polyneuropathy.
§ The term pneumonia is a grouping of the following terms: pneumonia, atypical pneumonia, bronchopneumonia, lobar pneumonia, bacterial pneumonia, fungal pneumonia, pneumonia influenza, and pneumococcal pneumonia.

EMPLICITI Prescribing Information, Table 4

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

Subgroup analyses were conducted for sex, race and age.

  • Sex: The risk of side effects was similar in men and women.
  • Race: The majority of patients were white. Differences in side effects among races could not be determined.
  • Age: The risk of a second primary cancer was higher in patients above 65 years of age compared to patients under 65 years of age. A second primary cancer refers to a new cancer in a person with a history of a different cancer.

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

The tables below summarize frequency of overall adverse events by sex and age group.

Table 4. Adverse Event with at Least 5 Percent Frequency Summary by Sex

 Male
N=266
Female
N=185
Total Subjects with an Event266 (100)183 (98.9)

Clinical Trial Data

The tables below summarize how many patients by age group were diagnosed with a second primary malignancy as well as the type of malignancy.

Table 5. Subjects with Second Primary Malignancy by Age

<65 years65 to <75 years≥75 years
E-Ld
N=133
Ld
N=137
E-Ld
N=119
Ld
N=121
E-Ld
N=66
Ld
N=59
4 (3)9 (6.6)13 (10.9)4 (3.3)9 (13.6)2 (3.4)

Clinical Trial Data

Table 6. Second Primary Malignancy Events by Age and Category

Category of malignancy, number of events65 to <75 years≥75 years
E=Ld
(N=119)
Ld
(N=121)
E=Ld
(N=66)
Ld
(N=59)
Skin6442
Hematological11a3c,d1a
Solid6b2c30

N’s represent the total number of subjects in each age sub-group
a This subject also had a non-melanoma skin malignancy and is also counted in that category of malignancy
b 2 events were diagnosed from screening tests
c 1 event was diagnosed from screening tests d 1 subject had 2 hematologic malignancies

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved EMPLICITI based primarily on evidence from a clinical trial of 646 patients with multiple myeloma. The trial was conducted at 230 sites in 21 countries in Europe, North America (including United States), Japan, Australia, and Israel.

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

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were enrolled in the clinical trial used to evaluate efficacy of the drug EMPLICITI.  In total, 385 men (60%) and 261 women (40%) participated in the clinical trial used to evaluate efficacy of the drug EMPLICITI.

Clinical Trial Data

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

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the EMPLICITI clinical trial. In total, 544 Whites (84%), 23 Black or African Americans (4%), 64 Asians (10%), 1 Native Hawaiian or Pacific Islander (<1%), 1 missing, (<1%), and 2 others (2%) participated in the clinical trial.

Clinical Trial Data

Table 1. Demographics of Efficacy Trials by Race

RaceNumber of PatientsPercentage
White54484%
Black or African American234%
Asian6410%
Native Hawaiian or Other Pacific Islander1<1%
Missing1<1%
Other132%

Clinical Trial Data

Figure 3 summarizes how many patients by age group were enrolled in the clinical trial.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the EMPLICITI clinical trial.  In total, 276 participants were below 65 years old (43%) and 370 participants were 65 and older (57%).

Who participated in the trials?

The table below summarizes demographics of the clinical trial.

Table 7. Baseline Demographics of Patients in the Clinical Trial

SubgroupEMPLICITI+Lenalidomide and Dexamethasone
N=321
Lenalidomide and Dexamethasone
N=325
Total
N=646
Sex, n (%)
Male192 (60)193 (59)385 (60)
Female129 (40)132 (41)261 (40)
Age Group, n (%)
< 65 years134 (42)142 (44)276 (43)
>=65 years187 (58)183 (56)370 (57)
Race, n (%)
White264 (83)280 (86)544 (84)
Black or African American13 (4)10 (3)23 (4)
Asian33 (10)31 (10)64 (10)
Native Hawaiian or Other Pacific Islander1 (<1)01 (<1)
Missing1 (<1)01 (<1)
Other9 (3)4 (1)13 (2)

Clinical Trial Data

How were the trials designed?

The benefits and side effects of EMPLICITI in combination with lenalidomide and dexamethasone were evaluated in a trial in patients with multiple myeloma who had received one to three prior therapies and had documented worsening of their cancer following their most recent therapy.

Eligible patients were randomized to receive either EMPLICITI in combination with lenalidomide and low-dose dexamethasone or lenalidomide and low-dose dexamethasone. Patients and healthcare practitioners knew which treatment was being administered. Treatment was administered in 4-week cycles until the cancer worsened or the patient experienced unacceptable side effects.

The efficacy of EMPLICITI was evaluated by measuring the amount of time before the cancer worsened.

How were the trials designed?

The efficacy and safety of EMPLICITI in combination with lenalidomide and dexamethasone were evaluated in a randomized, open-label trial in patients with multiple myeloma who had received one to three prior therapies and had documented progression following their most recent therapy.

Eligible patients were randomized in a 1:1 ratio to receive either EMPLICITI in combination with lenalidomide and low-dose dexamethasone or lenalidomide and low-dose dexamethasone. Treatment was administered in 4-week cycles until disease progression or unacceptable toxicity. EMPLICITI 10 mg/kg was administered intravenously each week for the first 2 cycles and every 2 weeks thereafter. Prior to EMPLICITI infusion, dexamethasone was administered as a divided dose: an oral dose of 28 mg and an intravenous dose of 8 mg. In the control group and on weeks without EMPLICITI, dexamethasone 40 mg was administered as a single oral dose weekly. Lenalidomide 25 mg was taken orally once daily for the first 3 weeks of each cycle. Assessment of tumor response was conducted every 4 weeks.

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

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Page Last Updated: 01/13/2016
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