Drug Trials Snapshot: ENSACOVE
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 ENSACOVE Prescribing Information for all 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).
ENSACOVE (ensartinib)
(En-sa-kowv)
Xcovery Holdings, Inc.
Approval date: December 18, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ENSACOVE is a prescription medicine used to treat adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received an ALK-inhibitor.
How is this drug used?
ENSACOVE is a tablet that is taken by mouth once a day.
Who participated in the clinical trials?
The FDA approved ENSACOVE based on the results from a clinical trial (NCT02767804/eXALT3) that enrolled 290 study participants adult patients with locally advanced (stage IIIB following prior chemotherapy or chemoradiation or not amenable to curative intent therapy) or metastatic ALK-positive NSCLC.
The safety and efficacy of ENSACOVE were both assessed using information from the eXALT3 trial; however, the number of patients shown in the description of efficacy findings may differ from the number of patients shown in the description of safety findings due to the different inclusion criteria used to assess efficacy. Safety was also assessed in a pooled population of patients from eXALT3 and three other studies of patients with locally advanced or metastatic ALK-positive NSCLC.
How were the trials designed?
ENSACOVE was evaluated in the eXALT3 trial, an open-label, randomized, active-controlled, multicenter study in adult patients with locally advanced or metastatic ALK-positive NSCLC. A total of 290 ALK-naive patients were randomized to ENSACOVE (n=143) or crizotinib (n=147) and included in the ITT population. A total of 289 patients (143 ENSACOVE, 146 crizotinib) were treated with at least one dose of study drug and included in the safety population. Randomization was stratified by prior chemotherapy (0 versus 1), Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 versus 2), presence of central nervous system (CNS) metastases (yes or no), and geographic region (Asia versus the rest of the world).
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female ALK-positive NSCLC patients with no prior ALK tyrosine kinase inhibitors (TKIs) were enrolled in the clinical trial used to evaluate the efficacy of ENSACOVE.
Figure 1. Baseline Demographics by Sex, ITT Population
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of ALK-positive NSCLC patients with no prior ALK TKIs by race enrolled in the clinical trial used to evaluate the efficacy of ENSACOVE.
Figure 2. Baseline Demographics by Race, ITT Population
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of ALK-positive NSCLC patients with no prior ALK TKIs by age enrolled in the clinical trial used to evaluate the efficacy of ENSACOVE.
Figure 3. Baseline Demographics by Age, ITT Population
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of ALK-positive NSCLC patients with no prior ALK TKIs by ethnicity enrolled in the clinical trial used to evaluate the efficacy of ENSACOVE.
Figure 4. Baseline Demographics by Ethnicity, ITT Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, ITT Population
| Demographic | ENSACOVE N=143 | Crizotinib N=147 | All N=290 | |
|---|---|---|---|---|
| Age, years | ||||
| Median | 54 | 53 | 54 | |
| Min, max | 25, 86 | 26, 90 | 25, 90 | |
| Age group, years, n (%) | ||||
| <65 | 116 (81.1) | 121 (82.3) | 237 (81.7) | |
| ≥65 | 27 (18.9) | 26 (17.7) | 53 (18.3) | |
| Sex, n (%) | ||||
| Female | 71 (49.7) | 70 (47.6) | 141 (48.6) | |
| Male | 72 (50.3) | 77 (52.4) | 149 (51.4) | |
| Race, n (%) | ||||
| Asian | 77 (53.8) | 84 (57.1) | 161 (55.5) | |
| Black or African American | 1 (0.7) | 3 (2.0) | 4 (1.4) | |
| Native Hawaiian or other Pacific Islander | 0 | 1 (0.7) | 1 (0.3) | |
| White | 62 (43.4) | 56 (38.1) | 118 (40.7) | |
| Other | 3 (2.1) | 3 (2.0) | 6 (2.1) | |
| Ethnicity, n (%) | ||||
| Hispanic or Latino | 15 (10.5) | 7 (4.8) | 22 (7.6) | |
| Not Hispanic or Latino | 127 (88.8) | 138 (93.9) | 265 (91.4) | |
| Unknown | 1 (0.7) | 2 (1.4) | 3 (1.0) | |
Source: Adapted from FDA Review
Abbreviations: ITT, intent-to-treat
What are the benefits of this drug?
The time participants lived without their disease progression (including death) more than doubled for those who received ENSACOVE than those in the crizotinib group: they had a median time to disease progression of 25.8 months compared to 12.7 months for participants in the crizotinib group.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 summarizes the results of the major efficacy outcome measures, progression-free survival (PFS) as determined by blinded independent central review according to RECIST v1.1.
Table 2. Efficacy Results, ITT Population
| Progression-Free Survivala,b,c | ENSACOVE N=143 | Crizotinib N=147 |
|---|---|---|
| Patients with event, n (%) | 59 (41) | 80 (54) |
| Median, months (95% CI) | 25.8 (21.8, NE) | 12.7 (9.2, 16.6) |
| Hazard ratio (95% CI) | 0.56 (0.40, 0.79) | |
| p-value d | 0.0007 | |
Source: Adapted from FDA Review
a Per RECIST version 1.1
b Based on BICR assessment
c Based on the prespecified interim analysis (1 July 2020)
>d Two-side p-value based on unstratified log-rank test, comparing to α=0.0174
Abbreviations: BICR, Blinded Independent Central Review; CI, confidence interval; ITT, intent-to-treat; NE, not estimable; RECIST, Response Evaluation Criteria in Solid Tumors
At the time of the PFS analysis, overall survival data were not mature with 27% deaths in the overall population.
Were there any differences in how well the drug worked in clinical trials among sex, race, age, and ethnicity?
- Sex: ENSACOVE worked similarly in females and males.
- Race: ENSACOVE worked better in Asian participants. There was no known biological rationale for a differential effect of ENSACOVE based on race.
- Age: ENSACOVE appeared to work better in participants younger than 65 years of age. The study did not include a sufficient number of participants 65 years of age and older. Therefore, differences in how ENSACOVE worked across age subgroups could not be determined.
- Ethnicity: The study did not include a sufficient number of Hispanic or Latino participants. Therefore, differences in how ENSACOVE worked among not Hispanic or Latino participants and Hispanic or Latino participants could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3 summarizes PFS hazard ratio by age, sex, and race subgroups for ALK-positive NSCLC. FDA issued a post-marketing commitment to request additional data to understand safety and effectiveness in adults older than 65 years of age and underrepresented racial and ethnic minority groups.
Table 3. Progression-Free Survival by Subgroup, ITT Population
| Subgroup | ENSACOVE | Crizotinib | Hazard Ratio (95% CI) | ||
|---|---|---|---|---|---|
| n/N | Median (Months) | n/N | Median (Months) | ||
| Age, years | |||||
| <65 | 116/237 | 25.8 | 121/237 | 11.1 | 0.48 (0.33, 0.70) |
| ≥65 | 27/53 | 18.8 | 26/53 | 29.5 | 1.20 (0.51, 2.86) |
| Sex | |||||
| Female | 71/141 | NE | 70/141 | 12.7 | 0.55 (0.33, 0.91) |
| Male | 72/149 | 25.5 | 77/149 | 9.3 | 0.55 (0.35, 0.88) |
| Race | |||||
| Asian | 77/161 | NE | 84/161 | 11.2 | 0.37 (0.22, 0.60) |
| Not Asian | 66/129 | 18.8 | 63/129 | 12.8 | 0.83 (0.51, 1.35) |
| Ethnicitya | |||||
| Hispanic or Latino | 15/22 | 18.5 | 7/22 | 16.6 | 0.75 (0.23, 2.50) |
| Not Hispanic or Latino | 127/265 | 25.8 | 138/265 | 12.7 | 0.55 (0.39, 0.80) |
Source: Adapted from FDA Review
a Fewer than 5 participants in the unknown subgroup
Abbreviations: CI, confidence interval; ITT, intent-to-treat
What are the possible side effects?
The most common side effects of ENSACOVE are rash; muscle or bone pain; itching; coughing; nausea; swelling (edema); vomiting; tiredness; fever; increased levels of liver and pancreatic enzymes; decreased white blood cell counts; changes in blood levels of phosphate, magnesium, sodium, and potassium; decreased hemoglobin in red blood cells; and increased blood bilirubin levels.
Serious safety issues with ENSACOVE include inflammation of the lungs, liver problems, skin reactions, slow heart rate, high blood sugar, vision problems, and allergic reactions to FD&C Yellow No. 5 (tartrazine).
What are the possible side effects (results of trials used to assess safety)?
Table 4 and Table 5 include the most common side effects and abnormal laboratory test results observed in the eXALT3 clinical trial.
Table 4. Adverse Reactions ≥10% in Patients With ALK-Positive Metastatic NSCLC Who Received ENSACOVE in eXALT3
| Adverse Reaction | ENSACOVE, N=143 | Crizotinib, N=146 | ||
|---|---|---|---|---|
| All Grades % | Grade 3 or 4 % | All Grades % | Grade 3 or 4 % | |
| Skin and subcutaneous tissue disorders | ||||
| Rasha | 66 | 12 | 10 | 0 |
| Pruritusb | 30 | 2.1 | 4.1 | 0 |
| Alopecia | 11 | 0 | 4.8 | 0 |
| Dry skin | 10 | 0.7 | 0.7 | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal painc | 36 | 1.4 | 20 | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Coughd | 31 | 0.7 | 16 | 0 |
| Gastrointestinal disorders | ||||
| Constipation | 31 | 0 | 26 | 0 |
| Nausea | 28 | 1.4 | 30 | 2.1 |
| Vomitinge | 16 | 0.7 | 32 | 0 |
| General disorders and administration site conditions | ||||
| Edemaf | 27 | 2.1 | 28 | 2.1 |
| Pyrexiag | 22 | 0.7 | 10 | 0.7 |
| Fatigueh | 21 | 0.7 | 14 | 1.4 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 15 | 0 | 12 | 1.4 |
| Infection and infestation | ||||
| Respiratory tract infection | 13 | 0.7 | 10 | 0 |
| Nervous system disorders | ||||
| Dizzinessi | 12 | 0.7 | 14 | 0.7 |
| Dysguesia | 10 | 0 | 11 | 0 |
| Vascular disorders | ||||
| Hemorrhagej | 10 | 1.4 | 4.8 | 0 |
Source: Adapted from ENSACOVE Prescribing Information
Adverse reactions were graded using NCI CTCAE version 4.03.
a Includes dermatitis, dermatitis acneiform, dermatitis bullous, drug eruption, eczema, exfoliative rash, palmar-plantar erythrodysaesthesia, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash morbilliform, rash papular, rash pruritic, rash pustular, skin exfoliation, and vulvovaginal rash
b Includes ear pruritus, eye pruritus, eyelids pruritus, lip pruritus, pruritus, and pruritus generalized
c Includes arthritis, spinal pain, myalgia, musculoskeletal pain, back pain, pain in extremity, neck pain, arthralgia, non-cardiac check pain, bone pain, musculoskeletal chest pain, and musculoskeletal discomfort
d Includes cough, productive cough, and upper-airway cough syndrome
e Includes vomiting and retching
f Includes eyelid edema, face edema, generalized edema, localized edema, edema, edema peripheral, gravitational edema, skin edema, eye edema, and periorbital edema
g Includes pyrexia and hyperthermia
h Includes fatigue and asthenia
i Includes dizziness, vertigo, and postural dizziness
j Includes hemoptysis, intracranial hemorrhage, gastrointestinal hemorrhage, hematuria, upper gastrointestinal hemorrhage, vaginal hemorrhage, gingival bleeding, vitreous hemorrhage, epistaxis, rectal hemorrhage, and anal hemorrhage
Abbreviations: ALK, anaplastic lymphoma kinase; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer
Table 5. Laboratory Abnormality Safety Results for Patients Who Received ENSACOVE in eXALT3
| Lab Abnormality | ENSACOVE, N=143 | Crizotinib, N=146 | ||
|---|---|---|---|---|
| All Grades % | Grade 3 or 4 % | All Grades % | Grade 3 or 4 % | |
| Chemistry | ||||
| Alanine aminotransferase increased | 73 | 5 | 74 | 8 |
| Alkaline phosphatase increased | 64 | 2.2 | 50 | 0.7 |
| Aspartate aminotransferase increased | 64 | 1.4 | 62 | 3.5 |
| Glucose increased | 49 | 5 | 35 | 0.7 |
| Albumin decreased | 46 | 0.7 | 56 | 1.4 |
| Phosphate decreased | 39 | 7 | 42 | 4.9 |
| Uric acid increased | 39 | 39 | 27 | 27 |
| Creatinine increased | 37 | 0 | 27 | 0 |
| Calcium decreased | 36 | 1.4 | 64 | 4.9 |
| Sodium decreased | 27 | 4.3 | 27 | 4.2 |
| Hematology | ||||
| Lymphocytes decreased | 57 | 7 | 47 | 5 |
| Hemoglobin decreased | 43 | 0.7 | 31 | 1.4 |
Source: Adapted from ENSACOVE Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The occurrence of side effects was similar in White and Asian patients. The number of patients of other races was small; therefore, differences in how the drug worked in other races could not be determined.
- Age: The occurrence of side effects was higher in patients 65 years of age and older.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
There was a higher incidence of serious side effects, and more frequent side effects leading to treatment discontinuations and dose modifications in patients 65 years or older as compared to those younger than 65 years. Side effects by sex, race, and age are summarized in Table 6, Table 7, and Table 8.
Table 6. Side Effects by Sex for Patients Who Received ENSACOVE in eXALT3
| Adverse Event | Male N=77 n (%) | Female N=71 n (%) |
|---|---|---|
| Patients with TEAEs | 71 (99) | 70 (99) |
| Patients with TEAEs Grade ≥3 | 35 (49) | 37 (52) |
| Serious TEAEs (SAEs) | 18 (25) | 15 (21) |
| Grade 5 (deaths due to TEAEs) | 1 (1.4) | 1 (1.4) |
Source: Adapted from FDA Review
Abbreviations: SAE, serious adverse event; TEAE, treatment-emergent adverse event
Table 7. Side Effects by Race for Patients Who Received ENSACOVE in eXALT3
| Adverse Event | White N=62 n (%) | Asian N=77 n (%) | Black N=0 n (%) | Multiple Races N=1 n (%) | Other N=3 n (%) |
|---|---|---|---|---|---|
| Patients with TEAEs | 60 (97) | 77 (100) | 0 | 1 (100) | 3 (100) |
| Patients with TEAEs Grade ≥3 | 33 (53) | 36 (47) | 0 | 1 (100) | 2 (67) |
| Patients with serious TEAEs | 14 (23) | 18 (23) | 0 | 1 (100) | 0 |
| Patients with fatal TEAEs | 1 (1.6) | 1 (1.3) | 0 | 0 | 0 |
Source: Adapted from FDA Review
Abbreviations: SAE, serious adverse event; TEAE, treatment-emergent adverse event
Table 8. Side Effects by Age for Patients Who Received ENSACOVE in exALT3
| Adverse Event | <65 Years N=116 n (%) | ≥65 Years N=27 n (%) |
| Patients with TEAEs | 115 (99) | 26 (96) |
| Patients with TEAEs Grade ≥3 | 54 (47) | 18 (67) |
| Patients with serious TEAEs | 23 (20) | 10 (37) |
| Patients with fatal TEAEs | 2 (1.7) | 0 (0) |
Source: Adapted from FDA Review
Abbreviations: SAE, serious adverse event; TEAE, treatment-emergent adverse event
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.