FDA approves third "tissue agnostic" cancer drug

  • FDA

  • Yael Waknine
  • Clinical Essentials
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  • The FDA has granted accelerated approval for entrectinib (Rozlytrek) to treat tumors positive for fusion in the neurotrophic tyrosine receptor kinase (NTRK) gene in patients aged ≥12 years.
    • Indicated for metastatic or unresectable disease with posttreatment progression or no therapeutic options. 
  • Entrectinib was also approved for the treatment of adults with metastatic, ROS1+ NSCLC.

Why this matters

  • Agents previously approved to target a genetic defect rather than tumor type include larotrectinib (Vitrakvi, for NTRK+ tumors) and pembrolizumab (Keytruda).
  • Prescribing information is available here.

Study design

  • Approval was based on a pooled analysis of data from 4 multicenter, single-arm, open-label trials: ALKA-372-001, STARTRK-1, STARTRK-2, and STARTRK-NG.
  • NTRK+ solid tumors: 54 patients with locally advanced (4%) or metastatic (96%) disease.
    • 10 tumor types: sarcoma; NSCLC; salivary gland, breast, thyroid, colorectal, neuroendocrine, pancreatic, and gynecologic cancers; and cholangiocarcinoma.
  • ROS1+ NSCLC: 53 patients (94% adenocarcinoma); 94% with metastatic disease and 43% with central nervous system (CNS) metastases.
  • Funding: Genentech.  

Key results

  • NTRK+ solid tumors: overall response rate (ORR), 57% (complete response, 7.4%; partial response, 50%).
    • Duration of response (DOR), ≥6, 9, and 12 months: 68%, 61%, and 45%, respectively.
    • ORR highest with salivary cancer (86%), breast cancer (83%), and NSCLC (70%).
  • ROS1+ NSCLC: ORR, 78% (complete response, 6%; partial response, 73%).
    • DOR, ≥9, 12, and 18 months: 70%, 55%, and 30%, respectively.
    • 5/7 with measurable CNS metastases showed intracranial response.


  • Serious adverse events may include congestive heart failure; CNS effects including cognitive impairment, mood disorders, dizziness; skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, and vision disorders.