Vitrakvi® Efficacy

Response rates across multiple tumor types in patients with NTRK* gene fusions (as assessed by a blinded independent review committee, N=55)1a

Learn about the efficacy of VITRAKVI™ (larotrectinib)
*CNS, central nervous system; CR, complete response; DOR, duration of response; IFS, infantile fibrosarcoma; IRC, independent review committee; NTRK, neurotrophic receptor tyrosine kinase; ORR, overall response rate; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors. aPrimary CNS* tumors were not included in the primary efficacy analysis. bIncludes 1 pediatric patient with unresectable IFS* who underwent resection following partial response and who remained disease-free at data cutoff.1

Study design: 55 adult and pediatric patients with unresectable or metastatic solid tumors with an NTRK gene fusion were included for the pooled efficacy analysis across LOXO-TRK-14001, SCOUT, and NAVIGATE. All patients were required to have progressed following systemic therapy for their disease, if available, or would have required surgery with significant morbidity for locally advanced disease.1

Major efficacy outcome measures: ORR and DOR,* as determined by a blinded IRC* according to RECIST* v1.1.1

DURATION OF AND TIME TO RESPONSE

Duration of response seen in clinical trials (n=41)1

Median Duration of Response Not Yet Reached at Time of Data Cutoff1

See efficacy for VITRAKVI™ (larotrectinib)
Plus sign denotes ongoing response.
Blinded IRC-assessed data.

Time to response2

Median time to response was 1.8 months (25/75 percentile: [1.77, 1.97])

Additional secondary endpoints included PFS2*

  • Median PFS not yet reached at time of data cutoff
*PFS, progression-free survival.

Important Safety Information

Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurological adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.

Please see additional Important Safety Information below

EFFICACY BY TUMOR TYPE

Response rates in various tumor types (as assessed by a blinded IRC, N=55)1

Efficacy Results by Tumor Type1

Plus sign denotes ongoing response. *NA, not applicable due to small numbers or lack of response; NE, not evaluable; PD, progressive disease; SD, stable disease. aObserved values at data cutoff, not a range.

EFFICACY ACROSS FUSION PARTNERS

Response rates across multiple NTRK gene fusion partners (N=55)1

Efficacy Results by NTRK Fusion Partner1

Plus sign denotes ongoing response. aFusion partners identified in the primary analysis set (N=55) may not represent all potential fusion partners. bDuration of response censored at the time of surgery for 1 pediatric patient with unresectable infantile fibrosarcoma who underwent resection following partial response and who remained disease-free at data cutoff. cObserved values at data cutoff, not a range.
See the Interactive PI

Indication

VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumors that:

  • have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation,
  • are metastatic or where surgical resection is likely to result in severe morbidity, and
  • have no satisfactory alternative treatments or that have progressed following treatment.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurological adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.

Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of patients.

Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.

Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily.

Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.

Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).

Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.

For important risk and use information about VITRAKVI, please see the full Prescribing Information.

You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088. For Bayer products you can report these directly to Bayer by clicking here.


References:

  • 1. VITRAKVI [package insert]. Stamford, CT: Loxo Oncology, Inc.; November 2018.
  • 2. Data on file, Stamford, CT: Loxo Oncology, Inc.; 2018.
  • 3. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion–positive cancers in adults and children. N Engl J Med. 2018;378(suppl):731-739.

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EFFICACY IN PEDIATRIC PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS HARBORING AN NTRK GENE FUSION1

VITRAKVI™ (larotrectinib) response rate aIn Study 3 (pediatric patients ages ≥1 month to 21 years),
7 patients had IFS and 5 had soft-tissue sarcoma.

Safety has been evaluated in pediatric patients (aged 1 month to 18 years)1

  • Adverse event incidences in the pediatric population (<18 years) were similar to those observed in the adult population1
    • The adverse events of nausea (37% versus 26% in adults), vomiting (47% versus 19% in adults), diarrhea (27% versus 17% in adults), leukopenia (27% versus 4% in adults), neutropenia (33% versus 2% in adults), transaminase elevations (33% versus 18% in adults), and cough (33% versus 18% in adults) were more frequent in pediatric patients compared to adults
    • A majority of these events were Grade 1 or 2 in severity and were resolved without larotrectinib dose modification or discontinuation

Demographics for the pediatric safety population1

Of 144 patients in the overall safety population who received VITRAKVI™1:

  • 21% of patients were pediatric1
    • 6 patients (4%) were <1 year of age; 10 patients (7%) were 1 to 5 years of age; 5 patients (3%) were 6 to 11 years of age; 9 patients (6%) were 12 to 17 years of age

IFS, infantile fibrosarcoma; NTRK, neurotrophic tyrosine receptor kinase; ORR, overall response rate.

TRIAL DESIGN FOR VITRAKVI® STUDIES

Approval was based on pooled results from 3 multicenter, open-label, single-arm, clinical studies1a

Review the clinical trials for VITRAKVI™ (larotrectinib)
  • 98% of patients had received prior treatment for their cancer, including surgery, radiotherapy, or systemic therapy1
  • Of these, 82% (n=45) received prior systemic therapy with a median of 2 prior systemic regimens and 35% (n=19) received ≥3 prior systemic regimens1
  • The safety population (N=176) included a larger group of patients from Studies 1, 2, and 3 because the safety assessment was not limited to patients with tumors harboring NTRK gene fusion1
The major efficacy outcome measures were ORR* and DOR* as determined by a blinded independent review committee according to RECIST* v1.1.1 *CNS, central nervous system; DOR, duration of response; NTRK, neurotrophic receptor tyrosine kinase; ORR, overall response rate; RECIST, Response Evaluation Criteria in Solid Tumors. aAll patients were required to have progressed following systemic therapy for their disease, if available, or would have required surgery with significant morbidity for locally advanced disease.1