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Drug Trials Snapshot: EXKIVITY

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic 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 healthcare provider about the benefits and risks of a drug.

Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the EXKIVITY Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).

Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).

EXKIVITY (mobocertinib)
(ex ki' vi tee)
Takeda Pharmaceuticals USA, Inc.
Original Approval date:
September 15, 2021


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

EXKIVITY is a kinase inhibitor used to treat adult patients with a type of lung cancer (non-small cell lung cancer or NSCLC) which:

  • has a specific gene mutation (EGFR exon 20 insertion mutations) and,
  • is locally advanced or has spread to other parts of the body (metastatic) and,
  • has progressed on or after platinum-based chemotherapy.

How is this drug used?

EXKIVITY is a capsule taken once a day by mouth. EXKIVITY may be taken with or without food.

Who participated in the clinical trials?

The FDA approved EXKIVITY based on evidence from a clinical trial of patients with EGFR exon 20 insertion mutation-positive locally advanced or metastatic NSCLC who received prior platinum-based chemotherapy. The trial was conducted at 70 sites in 9 countries (United States, Germany, Spain, Great Britain, Italy, China, Japan, South Korea and Taiwan). The same trial was used to assess the efficacy of EXKIVITY in 114 patients and the safety of EXKIVITY in 256 patients; therefore, the number of patients representing efficacy findings may differ from the number of patients representing safety findings due to different pools of study participants analyzed for efficacy and safety.

What are the benefits of this drug?

Approximately 28% of patients (32 of 114 patients) treated with EXKIVITY in the clinical study AP32788-15-101 had partial shrinkage of their cancer. Shrinkage lasted more than 6 months for 59% of patients who had a response to EXKIVITY.

EXKIVITY 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.

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

The table below summarizes the results of the major efficacy outcome measure, overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as evaluated by blinded independent central review (BICR).

Table 1. Efficacy Results in Patients with EGFR Exon 20 Insertion Mutation-Positive NSCLC Whose Disease Has Progressed on or after Platinum-Based Chemotherapy in Study AP32788-15-101

Efficacy Parameter

EXKIVITY
(n=114)

Overall Response Rate (ORR)a (95% CI)

28% (20, 37)b

Duration of Response (DOR)

Median (months)c, (95% CI)

17.5 (7.4, 20.3)

Patients with DOR ≥6 monthsd

59%

a Per BICR, CI = confidence interval
b All responses were partial responses
c Kaplan-Meier estimate using confirmed responses only
d Based on observed duration of response

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

  • Sex: EXKIVITY worked similarly in males and females.
  • Race: EXKIVITY worked similarly in White and Asian patients. There were few patients of other races.
  • Age: EXKIVITY 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?

Table 2. Overall response rates (ORR) in Study AP32788-15-101 Efficacy Population (N=114) by subgroup

Subgroup

N

ORR,
% (95% CI)

Age

<65 years

72

32 (21, 44)

≥ 65 years

42

21 (10, 37)

Sex

Female

75

29 (19, 41)

Male

39

26 (13, 42)

Race

Asian

68

31 (20, 43)

White

42

21 (10, 37)

Black

3

33 (1, 91)

Region

Asia

55

29 (18, 43)

Europe

6

33 (4, 78)

North America

53

26 (15, 40)

Overall

114

28 (20, 37)

What are the possible side effects?

The most common side effects observed with EXKIVITY include diarrhea, rash, nausea, mouth sores, vomiting, decreased appetite, infection of skin around the nails, tiredness, dry skin and muscle pain.

EXKIVITY can cause life-threatening heart-rate changes (QTc prolongation), inflammation of the lung (interstitial lung disease or pneumonitis) and heart problems (cardiac toxicity including heart failure).

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

Table 3. Adverse Reactions (≥10%) in Patients with EGFR Exon 20 Insertion Mutation-Positive NSCLC Whose Disease Has Progressed on or after Platinum-Based Chemotherapy in Study AP32788-15-101

Adverse Reaction

EXKIVITY
(N = 114)

All Grades*
(%)

Grade 3 or 4
(%)

Gastrointestinal Disorders

    Diarrhea

92

22

    Stomatitisa

46

4.4**

    Vomiting

40

2.6**

    Decreased appetite

39

0.9**

    Nausea

37

4.4**

    Decreased weight

21

0

    Abdominal painb

18

1.8**

    Gastroesophageal reflux disease

15

0

    Dyspepsia

11

0

Skin and Subcutaneous Tissue Disorders

    Rashc

78

1.8**

    Paronychiad

39

0.9**

    Dry skin

32

0

    ruritus

24

0.9**

    Alopecia

19

0

Musculoskeletal and Connective Tissue Disorders

    Musculoskeletal paine

34

2.6**

General Disorders and Administration Site Conditions

    Fatiguef

29

3.5**

Respiratory, Thoracic and Mediastinal Disorders

    Coughg

24

0

    Upper respiratory tract infectionh

16

0

    Dyspneai

15

4.4

    Rhinorrhea

13

0

Eye Disorders

    Ocular Toxicityj

11

0

Cardiac Disorders

    QTc interval prolongationk

10

3.5

    Hypertensionl

10

4.4**

Nervous System Disorders

    Headache

10

0

* Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 5)
** Events of Grade 3 only (no Grade 4 occurred)
a Stomatitis includes angular cheilitis, aphthous ulcer, cheilitis, mouth ulceration, mucosal inflammation, odynophagia, and stomatitis.
b Abdominal pain includes abdominal discomfort, abdominal pain, abdominal pain upper, abdominal tenderness, and gastrointestinal pain.
c Rash includes acne, dermatitis, dermatitis acneiform, rash, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, and urticaria.
d Paronychia includes nail bed tenderness, nail disorder, nail infection, onycholysis, and paronychia.
e Musculoskeletal pain includes arthralgia, back pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain.
f Fatigue includes asthenia, and fatigue.
g Cough includes cough, productive cough, and upper-airway cough syndrome.
h Upper respiratory tract infection includes nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, and upper respiratory tract infection.
i Dyspnea includes dyspnea, and dyspnea exertional.
j Ocular toxicity includes dry eye, eye pruritis, abnormal sensation in eye, eye discharge, blepharitis, trichiasis, conjunctival hemorrhage, vitreous floaters, blurred vision and corneal edema.
k QTc interval prolongation includes electrocardiogram QT prolonged, and ventricular arrhythmia.
l Hypertension includes blood pressure increased, and hypertension.

Clinically relevant adverse reactions in <10% of patients receiving EXKIVITY included edema (9%), acute kidney injury (8%), peripheral neuropathy (7%), palmar-plantar erythrodysaesthesia (4.4%), pneumonitis (2.6%) and cardiac failure (2.6%).

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

  • Sex: The occurrence of side effects was generally similar in men and women.
  • Race: A higher percentage of White patients reported Grades 3 to 4 Adverse Reactions than Asian patients. There were few patients enrolled in other race categories.
  • Age: The occurrence of serious and high-grade side effects was higher in patients 65 years and older as compared to those younger than 65 years of age.

Table 1. Overview of Adverse Reactions by Sex, Age, Race, Ethnicity, and Country in Patients with NSCLC Who Received EXKIVITY 160 mg Once Daily in Safety Population

 

Demographic Variable

EXKIVITY
N=256

All Patients
n (%)

All Grades
n/Ns (%)

Grades 3 to 4
n/Ns (%)

Sex, n (%)

Female

169 (66.0)

168/169 (99.4)

114/169 (67.5)

Male

87 (34.0)

87/87 (100)

50/87 (57.5)

Age group, years, n (%)

18 to <65 years

160 (62.5)

159/160 (99.4)

93/160 (58.1)

≥65 years

96 (37.5)

96/96 (100)

71/96 (74.0)

Race, n (%)

Asian

102 (39.8)

102/102 (100)

52/102 (51.0)

Black or African American

12 (4.7)

12/12 (100)

9/12 (75.0)

Unknown

3 (1.2)

3/3 (100)

2/3 (66.7)

White

139 (54.3)

138/139 (99.3)

101/139 (72.7)

Ethnicity, n (%)

Hispanic or Latino

12 (4.7)

11/12 (91.7)

9/12 (75.0)

Not Hispanic or Latino

231 (90.2)

231/231 (100)

151/231 (65.4)

Not reported

13 (5.1)

13/13 (100)

4/13 (30.8)

Country

United States

176 (68.8)

80/80 (100)

41/80 (51.2)

Non-United States

80 (31.2)

175/176 (99.4)

123/176 (69.9)

Source: FDA reviewer’s analysis
Abbreviation: N, number of patients in the safety population; n, number of patients with given characteristic; Ns, total number of patients in each category; NSCLC, non-small cell lung cancer
Safety population includes patients from studies AP32788-15-101 and TAK-788-1003 (Part 1) who received EXKIVITY at the recommended dose of 160 mg once daily.

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes how many men and women were enrolled in the clinical trial used to evaluate the efficacy and safety of EXKIVITY.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trial. In total, 39 (34%) men and 75 (66%) women participated in the efficacy population

Pie chart summarizing how many men and women were in the clinical trial. In total, 87(34%) men and 169(66%) women participated in the safety population of the clinical trial.

Source: Adapted from FDA Review

Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the efficacy and safety of EXKIVITY.

Figure 2. Baseline Demographics by Race

Pie chart summarizing how many White, Black, Asian, and Not Reported patients were in the clinical trial. In total, 42 (37%) white, 3 (3%) black, 68(60%), 1(1%) not reported patients participated in the efficacy population

Pie chart summarizing how many White, Black, Asian, and Not Reported patients were in the clinical trial. In total,  139 (54%) white, 12(5%) black, 102(40%) Asian, and 3(1%) not reported patients participated in the safety population of the clinical trial.

Source: Adapted from FDA Review

Figure 3 summarizes the percentage of patients by age group enrolled in the clinical trial used to evaluate the efficacy and safety of EXKIVITY.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many patients by age were in the clinical trial. In total, 72(63%) patients were less than 65 years of age, and 42(37%) patients were 65 years of age and older in the efficacy population.

Pie chart summarizing how many patients by age were in the clinical trial. In total, 160(63%) patients were less than 65 years of age and 96(63%) patients were 65 years of age or older that participated in the safety population of the clinical trial.

Source: Adapted from FDA Review

Who participated in the trials?

Table 4. Baseline Demographics and Disease Characteristics in the Efficacy and Safety Populations of Study AP32788-15-101

 

Efficacy Population
N = 114

Safety Population
N = 256

Sex, n (%)

    Female

75 (66)

169 (66)

    Male

39 (34)

87 (34)

Age at diagnosis (years), median [range]

60 [27, 84]

61 [24, 86]

    < 65 Years

72 (63)

160 (63)

    >= 65 Years

42 (37)

96 (38)

Race, n (%)

    Asian

68 (60)

102 (40)

    Black or African American

3 (3)

12 (5)

    White

42 (37)

139 (54)

    Not reported

1 (1)

3 (1)

Ethnicity, n (%)

    Hispanic or Latino

1 (1)

12 (5)

    Not Hispanic or Latino

113 (99)

231 (90)

    Not Reported

0

13 (5)

Region, n (%)

    Asia

55 (48)

70 (27)

    Europe

6 (5)

10 (4)

    North America

53 (47)

176 (69)

ECOG performance status at study entry, n (%)

    0

29 (25)

82 (32)

    1

85 (75)

174 (68)

Disease Stage at study entry, n (%)

    Stage IIIB

1 (1)

3 (1)

    Stage IV

113 (99)

244 (95)

    Missing

0

9 (4)

Histopathology at study entry, n (%)

    Adenocarcinoma

112 (98)

245 (96)

    Adenosquamous carcinoma

0

1 (<1)

    Non-Squamous

1 (1)

2 (<1)

    Squamous

1 (1)

4 (2)

    Other

0

4 (2)

Site involvement at study entry, n (%)

    Brain

40 (35)

 

    Bone

47 (41)

117 (46)

    Liver

24 (21)

 

    Lung

110 (97)

231 (90)

    Other

93 (82)

202 (79)

Smoking History, n (%)

    Current

2 (2)

3 (1)

    Former

31 (27)

 

    Never

81 (71)

167 (65)

    Unknown

0

1 (<1)

Number of Prior Lines of Therapy, median [range]

2 [1, 7]

 

    1

47 (41)

 

    2

36 (32)

 

    ≥3

31 (27)

 

Prior EGFR TKI therapy, n (%)

    No

85 (75)

 

    Yes

29 (25)

 

Prior PD-1 or PD-L1 therapy, n (%)

    No

66 (58)

 

    Yes

48 (42)

 

ECOG = Eastern Cooperative Oncology Group; EGFR = epidermal growth factor receptor; TKI = tyrosine kinase inhibitor; PD-1 = programmed cell death protein 1; PD-L1 = programmed cell death-ligand 1

How were the trials designed?

EXKIVITY was evaluated in an international, open-label, single arm, multicohort clinical trial (Study AP32788-15-101) including 114 patients with EGFR exon 20 insertion mutation-positive metastatic or locally advanced NSCLC whose disease had progressed on or after platinum-based chemotherapy. Patients had histologically or cytologically confirmed locally advanced or metastatic disease (Stage IIIB or IV) and a documented EGFR exon 20 insertion mutation based on local testing. Patients received EXKIVITY at a dose of 160 mg once daily until disease progression or intolerable toxicity. The major efficacy outcome measure was overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as evaluated by blinded independent central review (BICR). Additional efficacy outcome measures included duration of response (DOR) by BICR.

How were the trials designed?

eStudy AP32788-15-101 was international, open-label, single arm, dose escalation and dose expansion study of EXKIVITY. This study included a dose-escalation phase (Part 1), which established the recommended Phase 2 dose (RP2D) of mobocertinib, followed by an expansion phase in 7 distinct disease cohorts treated at the RP2D (Part 2), and an extension cohort (Part 3). In the dose escalation phase, the doses ranged from 5 mg to 180 mg daily. The extension cohort (Part 3) included patients with locally advanced or metastatic non-small cell lung cancer, who were treated at the RP2D of 160 mg once daily, and who had been previously treated with at least one prior line of therapy. The efficacy population (N=114) included patients from all 3 parts with metastatic NSCLC with EGFR Exon 20 insertion mutations who had previously been treated with platinum-based chemotherapy and were administered the recommended dose of 160 mg daily (Part 1 [n = 6]; Expansion Cohort 1 of Part 2 [n = 22]; and Part 3 [n = 86]).

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 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.

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