Initial US Approval

  • 20191

Indications

Metastatic ROS1+ NSCLC:

  • Treatment of adult patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.1

Metastatic NTRK+ Solid Tumors:

  • Treatment of adult and pediatric patients older than 1 month of age with solid tumors that1:
    • Have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, as detected by an FDA-approved test without a known acquired resistance mutation,
    • Are metastatic or where surgical resection is likely to result in severe morbidity, and
    • Have progressed following treatment or have no satisfactory alternative therapy.
    • This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Recommended Dose/Route

  • Entrectinib 600 mg orally once daily with or without food1
Entrectinib Dose Reductions for Adverse Reactions

Entrectinib Dose Reductions for Adverse Reactions

Pivotal Study

STARTRK-1 (NCT02097810) and STARTRK-2 (NCT02568267), and ALKA-372-001 (EudraCT, 2012–000148–88) - Integrated Analysis2,3

  • Key Inclusion Criteria: Eligible patients were required to have ROS1 fusion–positive, locally advanced or metastatic measurable NSCLC at baseline (locally assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.118) and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2.1
  • Treatment: Entrectinib 600 mg orally once daily until documented radiographic disease progression (PD), unacceptable toxicity, or withdrawal of consent.1
Entrectinib Efficacy Data

Entrectinib: Efficacy Data

Entrectinib Efficacy Data ROS1

Entrectinib Efficacy Data ROS1

Safety

STARTRK-1 (NCT02097810) and STARTRK-2 (NCT02568267), and ALKA-372-001 (EudraCT, 2012–000148–88) - Integrated Analysis2,3

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were fatigue (48%), constipation (46%), dysgeusia (44%), edema (40%), dizziness (38%), diarrhea (35%), nausea (34%), dysesthesia (34%), dyspnea (30%), myalgia (28%), pyrexia (21%), arthralgia (21%), and vision disorders (21%).
  • Common Laboratory Abnormalities (≥20%): The most frequently reported any grade laboratory abnormalities were increased creatinine (73%), anemia (67%), hyperuricemia (52%), increased AST (44%), lymphopenia (40%), increased ALT (38%), hypernatremia (35%), hypocalcemia (34%), hypophosphatemia (30%), neutropenia (285), increased lipase (28%), hypoalbuminemia (28%), increased amylase (26%), hypercalcemia (25%), and increased alkaline phosphatase (25%).
  • Dosage Interruption Due to AEs: 46%1
  • Dosage Reduction Due to AEs: 29%1
  • Permanent Discontinuation Due to AEs: 9%1
Entrectinib: Most Common Adverse Events of Grade 3 or 4

Entrectinib: Most Common Adverse Events of Grade 3 or 4

References

  1. ROZLYTREK (entrectinib). Prescribing information. Genentech USA, Inc.; 2024. Accessed December 10, 2024. https://www.gene.com/download/pdf/rozlytrek_prescribing.pdf
  2. Drilon A, Siena S, Dziadziuszko R, et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020;21(2):261-270.
  3. Drilon A, Chiu CH, Fan Y, et al. Long-term efficacy and safety of entrectinib in ROS1 fusion-positive NSCLC. JTO Clin Res Rep. 2022;3(6):100332.
  4. Martineau C, Turcotte MK, Otis N, et al. Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review. Support Care Cancer. 2022;30(12):10471-10482. doi:10.1007/s00520-022-07401-y
  5. Lim JSJ, Tan DSP. TRK inhibitors: managing on-target toxicities. Ann Oncol. 2020;31(9):1109-1111. doi:10.1016/j.annonc.2020.06.010
  6. Liu D, Flory J, Lin A, et al. Characterization of on-target adverse events caused by TRK inhibitor therapy. Ann Oncol. 2020;31(9):1207-1215. doi:10.1016/j.annonc.2020.05.006