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: ROZLYTREK
  1. Drug Approvals and Databases

Drug Trials Snapshots: ROZLYTREK

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.

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 ROZLYTREK Prescribing Information for complete information.

ROZLYTREK (entrectinib)
roz lye' trek
Genentech, Inc.
Approval date: August 15, 2019


What is the drug for?

ROZLYTREK is a drug used to treat adult patients with a type of non-small cell lung cancer (NSCLC) which:

  • is caused by an abnormal ROS1 gene and,
  • has spread to other parts of the body (metastatic).

How is this drug used?

ROZLYTREK is a capsule taken by mouth once a day.

What are the benefits of this drug?

Forty (78%) of 51 patients with NSCLC who received ROZLYTREK experienced complete or partial shrinkage of their tumors. Tumor shrinkage lasted more than 12 months for 55% % of those patients.

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

The table below summarizes efficacy results based on overall response rate. Efficacy was assessed in 51 adult patients from three trials with metastatic NSCLC whose tumors were ROS1 positive.

Table 2. Efficacy Results in ROS1-Positive NSCLC Patients per BICR Assessment

Efficacy Parameters ROZLYTREK
N= 51
Overall Response Rate (95% CI) 78% (65, 89)
    Complete Response     6%
    Partial Response     73%
Duration of Response (DOR)* N=40
    Range (months) 1.8,36.8+
    % DOR ≥9 months 70%
    % DOR ≥12 months 55%
    % DOR ≥18 months 30%

BIRC= blinded independent review committee; Confidence Interval (CI) calculated using the Clopper-Pearson method.
Response duration were based on additional 5 months’ follow-up after the primary analysis of ORR.* Observed DOR
+ denotes ongoing response

ROZLYTREK Prescribing Information

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

The difference in how well the drug worked in clinical trials among sex, race and age groups could not be determined because of the small sample sizes.

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

The table below summarizes overall response rate by sex, race and age subgroups. Results should be interpreted with caution given the small sample size overall, and the limited number of patients in each subgroup.

Table 3. Subgroup Analyses Based on Overall Response Rate

Subgroup Patients, n Responders, n (ORR, %) 95% CI
  Men 17 14 (82.4%) (56.6%, 96.2%)
  Women 34 26 (76%) (58.8%, 89.3%)
  Asian 19 16 (84%) (60.4%, 96.6%)
  White 29 22 (75.9%) (56.5%, 89.7%)
  >=65 10 8 (80.0%) (44.4%, 97.5%)
  <65 41 32 (78.0%) (62.4%, 89.4%)
  USA 14 11 (78.6%) (49.2%, 95.3%)
  Non‐USA 37 29 (78.4%) (61.8%, 90.2%)

CI = confidence interval

FDA Review

What are the possible side effects?

ROZLYTREK may cause serious side effects including congestive heart failure, nervous system problems, bone fractures, liver toxicity, increased uric acid in the blood, heart rhythm problems (because of changes in heart electrical activity called QT prolongation) and vision problems.

The most common side effects of ROZLYTREK are tiredness, constipation, taste changes, body swelling, dizziness, and diarrhea.

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

The table below summarizes adverse reactions that occurred in ≥10% of patients treated with ROZLYTREK combining data from four clinical trials.

Table 4. Adverse Reactions Occurring in ≥10% of Patients Treated with ROZLYTREK

Adverse Reactions ROZLYTREK
All Grades (%) Grade ≥ 3* (%)
Fatigue1 48 5
Edema2 40 1.1
Pyrexia 21 0.8
Constipation 46 0.6
Diarrhea 35 2.0
Nausea 34 0.3
Vomiting 24 0.8
Abdominal pain3 16 0.6
Nervous System
Dysgeusia 44 0.3
Dizziness4 38 0.8
Dysesthesia5 34 0.3
Cognitive effects6 27 4.5
Peripheral sensory neuropathy7 18 1.1
Headache 18 0.3
Ataxia8 17 0.8
Sleep9 14 0.6
Mood disorders10 10 0.6
Respiratory, Thoracic and Mediastinal
Dyspnea 30 6*
Cough 24 0.3
Metabolism and Nutritional
Increased Weight 25 7
Decreased appetite 13 0.3
Dehydration 10 1.1
Musculoskeletal and Connective Tissue
Myalgia11 29 1.1
Arthralgia 21 0.6
Muscular weakness 12 0.8
Back pain 12 1
Pain in extremity 11 0.3
Metabolism and Nutritional
Increased weight 25 7
Decreased appetite 13 0.3
Dehydration 10 1.1
Vision disorders12 21 0.8
Urinary tract infection 13 2.3
Lung infection13 10 6*
Hypotension14 18 2.8
Skin and Subcutaneous Tissue
Rash15 11 0.8

* Grades 3 – 5, inclusive of fatal adverse reactions, including 2 events of pneumonia and 2 events of dyspnea.
1Includes fatigue, asthenia
2Includes face edema, fluid retention, generalized edema, localized edema, edema, edema peripheral, peripheral swelling
3Includes abdominal pain upper, abdominal pain, lower abdominal discomfort, abdominal tenderness
4Includes dizziness, vertigo, dizziness postural 5Includes paresthesia, hyperesthesia, hypoesthesia, dysesthesia, oral hypoesthesia, palmar-plantar erythrodysesthesia, oral paresthesia, genital hypoesthesia
6Includes amnesia, aphasia, cognitive disorder, confusional state, delirium, disturbance in attention, hallucinations, visual hallucination, memory impairment, mental disorder, mental status changes
7Includes neuralgia, neuropathy peripheral, peripheral motor neuropathy, peripheral sensory neuropathy
8Includes ataxia, balance disorder, gait disturbances
9Includes hypersomnia, insomnia, sleep disorder, somnolence
10Includes anxiety, affect lability, affective disorder, agitation, depressed mood, euphoric mood, mood altered, mood swings, irritability, depression, persistent depressive disorder, psychomotor retardation
11Includes musculoskeletal pain, musculoskeletal chest pain, myalgia, neck pain
12 Includes blindness, cataract, cortical cataract, corneal erosion, diplopia, eye disorder, photophobia, photopsia, retinal hemorrhage, vision blurred, visual impairment, vitreous adhesions, vitreous detachment, vitreous floaters
13 Includes lower respiratory tract infection, lung infection, pneumonia, respiratory tract infection
14 Includes hypotension, orthostatic hypotension
15 Includes rash, rash maculopapular, rash pruritic, rash erythematous, rash papular

The table below summarizes laboratory abnormalities that occurred in ≥ 20% patients treated with ROZLYTREK.

Table 5. Laboratory Abnormalities (≥ 20%) Worsening from Baseline in Patients Receiving ROZLYTREK (safety population)

Laboratory Abnormality ROZLYTREK
All Grades (%)1 Grade 3 or 4 (%)1
  Anemia 67 9
  Lymphopenia 40 12
  Neutropenia 28 7
  Increased creatinine2 73 2.1
  Hyperuricemia 52 10
  Increased AST 44 2.7
  Increased ALT 38 2.9
  Hypernatremia 35 0.9
  Hypocalcemia 34 1.8
  Hypophosphatemia 30 7
  Increased lipase 28 10
  Hypoalbuminemia 28 2.9
  Increased amylase 26 5.4
  Hyperkalemia 25 1.5
  Increased alkaline phosphatase 25 0.9
  Hyperglycemia3 NE3 3.8

AST: Aspartate Aminotransferase; ALT: Alanine Aminotransferase

1 Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available which ranged from 111 to 346 patients.
2 Based on NCI CTCAE v5.0
3 NE = Not evaluable. Grade 1 and 2 could not be determined per NCI CTCAE v5.0, as fasting glucose values were not collected

ROZLYTREK 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: The majority patients in the clinical trial were White or Asian. Differences in side effects among races could not be determined.
  • Age: The majority of patients in the clinical trial were younger than 65 years of age. Differences in side effects between patients below and above 65 years of age could not be determined.

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

Table 6 summarizes selected adverse events that occurred in the clinical trials by subgroups.

Table 6. Subgroup Analysis of Adverse Events (safety population)

Sex Race Age
<65 years n=265
≥65 years
Any Adverse Event 99 99 100 99 100 100 99
Serious Adverse Event 39 37 40 48 39 40 33

Clinical Trial Data


Who participated in the clinical trials?

The FDA approved ROZLYTREK based on the evidence from four clinical trials of patients with various types of solid tumors: Trial 1 (EudraCT 2012-000148-88), Trial 2 (NCT02097810), Trial 3 (NCT02568267), and Trial 4 (NCT02650401). The trials were conducted in the United States, Europe and Asia/Pacific region.

A subgroup of 51 patients with NSCLC from Trials 1, 2 and 3 that provided data characterizing the benefit of ROZLYTREK (efficacy population) is presented in Table 7 under MORE INFO.

All 355 patients (regardless of tumor types) from the four trials that provided data for the side effects of ROZLYTREK (safety population) are presented below.

Figure 1 below summarizes how many patients were in the clinical trials by sex.

Figure 1. Baseline Demographics by Sex (safety population)

Pie chart summarizing how many males and females were in the clinical trials. In total, 161 (45%) males and 194 (55%) females participated in the clinical trial.)

Clinical Trial Data

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

Figure 2. Baseline Demographics by Race (safety population)

Pie chart summarizing the percentage of patients by race enrolled in the clinical trial. In total, 235 (66%) White, 82 (23%) Asian,  16 (5%) Black or African American, and 22 (6%) Other patients participated in the clinical trials.)

Clinical Trial Data

Table 1. Demographics of Trial by Race (safety population)

Race Number of Patients Percentage
White 235 66
Black or African American 16 5
Asian 82 23
Not Reported 22 5

Clinical Trial Data

Figure 3 below summarizes the percentage of patients in the clinical trials by age.

Figure 3. Baseline Demographics by Age (safety population)

Pie chart summarizing how many individuals of certain age groups were enrolled in the clinical trial. In total, 265 patients were less than 65 years old (75%) and 90 patients were 65 years and older (25%).

Clinical Trial Data

Who participated in the trials?

Table 7 below summarizes patient demographics for the efficacy population of patients with ROS1-positive NSCLC and for the safety population of 355 patients who received at least one dose of ROZLYTREK irrespective of tumor type.

Table 7. Baseline Demographics of Patients in the Clinical Trials

Demographic Parameter Efficacy Population
n (%)
Safety Population
n (%)
Sex, n (%)
Men 17 (33) 161 (45)
Women 34 (67) 194 (55)
Race, n (%)
White 29 (57) 235 (66)
Black or African American 3 (6) 16 (4.5)
Asian 19 (37) 82 (23)
Not Reported/Other 0 21 (4.5)
Age (years)
Range 27,72 4,86
Median 53 55
Age Group, n (%)
<65 years 10 (20) 265 (75)
≥65 years 41 (80) 90 (25)
Ethnicity, n (%)
Hispanic 2 (4) 10 (3)
Non-Hispanic 38 (75) 264 (89)
Unknown/Not Reported 11 (22) 23 (8)
Geographic Region, n (%)
North America 14 (28) 180 (51)
Europe 19 (36) 102 (29)
Asia/Pacific 18 (36) 73 (20)

Clinical Trial Data

How were the trials designed?

The side effects of ROZLYTREK for NSCLC were evaluated in all patients enrolled in four clinical trials, and the benefit was evaluated in a subgroup of patients enrolled in three clinical trials.

Most adults received 600mg ROZLYTREK orally once a day until either tumor progression or intolerable side effects.

The benefit of ROZLYTREK for the treatment of NSCLC was evaluated by measuring the percentage of patients who achieved complete or partial shrinkage of their tumors (overall response rate) and by measuring the duration of that benefit (duration of response).

How were the trials designed?

There were three single-arm, open-label trials that provided data to evaluate the efficacy ROZLYTREK for patients with recurrent or metastatic ROS-1 positive NSCLC. The majority of the 51 patients received ROZLYTREK 600 mg orally once daily until unacceptable toxicity or disease progression.

The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as determined by a blinded independent review committee (BIRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Safety assessment was done on all patients from these three trials who received at least one dose of ROZLYTREK and one additional trial that enrolled pediatric and adult patients 4 to 20 years of age.


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.


Back to Drug Trials Snapshots

Back to Top