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

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 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

CI = confidence interval

FDA Review

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

^* 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)

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 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)

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

Clinical Trial Data

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.