Reply to Yap et al: re: Biopsy-Derived Biomarkers in Phase I Trials: Building Confidence in Drug Development

Reply to Yap et al

 ....The examples of poly (ADP-ribose) polymerase inhibitors are specifically mentioned in the correspondence.³ As noted in our original article, the maximum-tolerated dose, 400 mg twice daily, was subsequently used for further development.⁴ This dose and schedule were not based on the limited data from serial tumor biopsies (four patients at 200 to 400 mg, all with evidence of target inhibition) presented in that study. Notably, there was an apparent relationship between dose and response in BRCA-mutant patients with ovarian cancer, with greatest efficacy at the dose of 400 mg twice daily. Thus, the pharmacodynamic studies, although scientifically elegant, did not impact the choice of dose or the decision to advance the drug......

Related Article

• CORRESPONDENCE: Biopsy-Derived Biomarkers in Phase I Trials: Building Confidence in Drug Development

  • Timothy A. Yap,
  • Udai Banerji,
  • Johann S. de Bono,
  • and Paul Workman

  JCO JCO670075; published online on May 2, 2016;
  • [Full Text]
  • [PDF]

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Related Article

• CORRESPONDENCE: Biopsy-Derived Biomarkers in Phase I Trials: Building Confidence in Drug Development

  • Timothy A. Yap,
  • Udai Banerji,
  • Johann S. de Bono,
  • and Paul Workman

  JCO JCO670075; published online on May 2, 2016;
  • [Full Text]
  • [PDF]