For US Healthcare Professionals Only

Alt tag

ABOUT VITRAKVI®

DISEASE EDUCATION

TRK FUSION PROTEINS

MOD/MOA

NTRKa GENE FUSION:

An important driver in multiple tumor types1-3

NTRK gene fusions have been found to be the oncogenic driver across 25 adult and pediatric solid tumor types.1-4

Graphic of NTRK gene fusion in multiple solid tumor types
Alt tag

GI CANCERSa

Alt tag

THYROID

Alt tag

LUNG

Alt tag

CNS CANCERSb

Alt tag
Alt tag

SARCOMA

Alt tag

SALIVARY GLAND
CANCERSc

Alt tag

PEDIATRIC CANCERSd

MULTIPLE TUMOR TYPES
ONE KEY ONCOGENIC DRIVER

aCNS, central nervous system; GI, gastrointestinal; NTRK, neurotrophic receptor tyrosine kinase.

NTRK GENE FUSIONS ARE AN IMPORTANT ONCOGENIC DRIVER FOR TRK* FUSION CANCER2,3

NTRK Gene Fusions Lead to the Formation of Oncogenic TRK Fusion Proteins1

Formation of oncogenic TRK fusion proteins in NTRK gene fusion

*TRK, tropomyosin receptor kinase.

In TRK fusion cancer, the NTRK gene (NTRK1, NTRK2, and NTRK3) fuses with an unrelated gene.2,5,6

This fusion causes the expression of TRK fusion proteins, which results in cell proliferation and tumor growth.7

 

VITRAKVI: THE TRK INHIBITOR THAT WAS EXCLUSIVELY DESIGNED TO INHIBIT TRK1

How VITRAKVI works in TRK fusion cancer1

VITRAKVI was exclusively designed to inhibit against the TRK family of proteins (TRKA, TRKB, and TRKC).1

In in vitro and in vivo tumor models, VITRAKVI demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins.1

TRK fusion proteins can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines.1

VITRAKVI is approved under accelerated approval based on overall response rate and duration of response. Continued approval for VITRAKVI may be contingent upon verification and description of clinical benefit in confirmatory trials.1

Mechanism of Action: VITRAKVI Exclusively Targets TRK Kinases8

Depiction of human kinome with specific emphasis on TRK family of kinases

The image above is a depiction of the human kinome, with specific emphasis placed on the TRK family of kinases.8

Learn About Efficacy
Alt tag

Learn About Efficacy

CNS, central nervous system; GI, gastrointestinal; NTRK, neurotrophic tyrosine receptor kinase; TRK, tropomyosin receptor kinase.

References

  • VITRAKVI [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; November 2023. Return to content
  • Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25-34. Return to content
  • Okimoto RA, Bivona TG. Tracking down response and resistance to TRK inhibitors. Cancer Discov. 2016;6(1):14-16. Return to content
  • Data on file. Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ. Return to content
  • Kumar-Sinha C, Kalyana-Sundaram S, Chinnaiyan AM. Landscape of gene fusions in epithelial cancers: seq and ye shall find. Genome Med. 2015;7:129. doi:10.1186/s13073-015-0252-1. Return to content
  • Latysheva NS, Oates ME, Maddox L, et al. Molecular principles of gene fusion mediated rewiring of protein interaction networks in cancer. Mol Cell. 2016;63(4):579-592. Return to content
  • Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1(2):e000023. doi:10.1136/esmoopen-2015-000023. Return to content
  • Brose M, Bauer TM, Burris HA III, et al. LOXO-101, a selective pan-TRK inhibitor for patients with TRK-alterations. Poster presented at: 15th International Thyroid Congress; October 18-23, 2015; Lake Buena Vista, FL. Presentation 386. Return to content
Expand Close
Expand Close

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.

Select patients for therapy based on an FDA-approved test.

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

Warning and Precautions

  • Central Nervous System Effects: Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances.

    In patients who received VITRAKVI, all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 42% with Grades 3-4 in 3.9% of patients.

    Cognitive impairment occurred in 11% of patients. The median time to onset of cognitive impairment was 5.6 months (range: 2 days to 41 months). Cognitive impairment occurring in ≥1% of patients included memory impairment (3.6%), confusional state (2.9%), disturbance in attention (2.9%), delirium (2.2%), cognitive disorders (1.4%), and Grade 3 cognitive adverse reactions occurred in 2.5% of patients. Among the 30 patients with cognitive impairment, 7% required a dose modification and 20% required dose interruption.

    Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.9 months (range: 1 day to 40.5 months). Mood disorders occurring in ≥1% of patients included anxiety (5%), depression (3.9%), agitation (2.9%), and irritability (2.9%). Grade 3 mood disorders occurred in 0.4% of patients.

    Dizziness occurred in 27% of patients, and Grade 3 dizziness occurred in 1.1% of patients. Among the 74 patients who experienced dizziness, 5% of patients required a dose modification and 5% required dose interruption.

    Sleep disturbances occurred in 10% of patients. Sleep disturbances included insomnia (7%), somnolence (2.5%), and sleep disorder (0.4%). There were no Grade 3-4 sleep disturbances. Among the 28 patients who experienced sleep disturbances, 1 patient each (3.6%) required a dose modification or dose interruption.

    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 dosage when resumed.

  • Skeletal Fractures: Among 187 adult patients who received VITRAKVI across clinical trials, fractures were reported in 7% and among 92 pediatric patients, fractures were reported in 9% (N=279; 8%). Median time to fracture was 11.6 months (range 0.9 to 45.8 months) in patients followed per fracture. Fractures of the femur, hip or acetabulum were reported in 4 patients (3 adult, 1 pediatric). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement. VITRAKVI treatment was interrupted due to fracture in 1.4% patients.

    Promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures.

  • Hepatotoxicity: Hepatotoxicity including drug induced liver injury (DILI) has been reported in patients taking VITRAKVI.

    In patients who received VITRAKVI, increased AST of any grade occurred in 52% of patients and increased ALT of any grade occurred in 45%. Grade 3-4 increased AST or ALT occurred in 3.1% and 2.5% of patients, respectively. The median time to onset of increased AST was 2.1 months (range: 1 day to 4.3 years). The median time to onset of increased ALT was 2.3 months (range: 1 day to 4.2 years). Increased AST and ALT leading to dose modifications occurred in 1.4% and 2.2% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 3 (1.1%) of patients.

    There have been reports in adult patients from clinical studies and post-marketing cases of Grade ≥ 2 increases in ALT and/or AST with increases in bilirubin ≥ 2 x ULN.

    Obtain liver function tests (ALT, AST, ALP and bilirubin) before initiation of VITRAKVI and monitor every 2 weeks during the first two months of treatment, then monthly thereafter, or more frequently following the occurrence of Grade 2 or greater AST or ALT elevation. Temporarily withhold, reduce the dose, or permanently discontinue VITRAKVI based on severity.

  • 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.

Adverse Reactions

  • The most common adverse reactions (≥20%), including laboratory abnormalities, were: increased AST (52%), increased ALT (45%), anemia (42%), musculoskeletal pain (42%), fatigue (36%), hypoalbuminemia (36%), neutropenia (36%), increased alkaline phosphatase (34%), cough (32%), leukopenia (28%), constipation (27%), diarrhea (27%), dizziness (27%), hypocalcemia (25%), nausea (25%), vomiting (25%), pyrexia (24%), lymphopenia (22%) and abdominal pain (21%).

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. For coadministration with moderate CYP3A4 inhibitors, monitor for adverse reactions more frequently and reduce the dosage based on severity. For coadministration with moderate CYP3A4 inducers, modify dose as recommended.

Use in Specific Populations

  • 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.

© 2024 Bayer. All rights reserved. Bayer, the Bayer Cross, and VITRAKVI are registered trademarks of Bayer, and Access Services by Bayer is a trademark of Bayer. All other trademarks are the property of their respective owners.

 

This site is intended for US audiences only.

Site last updated on 10/2024

© 2024 Bayer. All rights reserved. Bayer, the Bayer Cross, and VITRAKVI are registered trademarks of Bayer, and Access Services by Bayer is a trademark of Bayer. All other trademarks are the property of their respective owners.

 

This site is intended for US audiences only.

 

Site last updated on 10/2024