Author of

• 12648

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  P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12659

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    P3.11-011 - Serum albumin as a potential pharmacodynamic biomarker in patients treated with the anti-hepatocyte growth factor monoclonal antibody ficlatuzumab (ID 1067)

    09:30 - 09:30  |  Author(s): K. McKee
    • Abstract

    Background
    Ficlatuzumab is an anti-hepatocyte growth factor (HGF) monoclonal antibody (mAb) being tested in clinical trials for cancer. Hypoalbuminemia has been observed in these trials, as well as in trials with other HGF/c-Met inhibitory mAbs. The relationship between serum albumin (SA) and ficlatuzumab treatment is examined.

    Methods
    Ficlatuzumab was studied in P05538, a first-in-human dose escalation trial; in P05670, a dose ranging trial investigating the pharmacodynamic (PD) effect of ficlatuzumab; and in P06162, a phase II study in combination with gefitinib (FG arm) versus gefitinib alone (G arm) in NSCLC patients. Patient data from these studies were evaluated longitudinally for peripheral edema, changes in SA, serum Ca[2+] (Ca), liver function tests (LFTs), prothrombin time (PT) and proteinuria.

    Results
    In P05538, all 23 evaluable patients had SA decrease with median change to nadir of -29% (-46 to -11%) and median nadir SA level of 25 g/L (15 to 33 g/L). In P05670, all 19 evaluable patients had decreased SA, with median change to nadir of -20% (-49 to -7%) and median nadir SA level of 31 g/L (14 to 40 g/L). In P06162, 88 of 90 (98%) evaluable patients in FG arm experienced SA decrease, with a median nadir change of -27% (range -62 to 8%). No significant SA changes were observed in the G arm. LFTs and PT were not significantly changed in any of the trials. Peripheral edema was observed in 52%, 32%, 38%, and 4% of the patients in P05538, P05670, FG, and G arms of P06162, respectively. In P06162, low Ca laboratory findings (not corrected for albumin) were reported in 72% of patients, with median change to nadir of -11% (-24% to 5%). Changes in uncorrected Ca were secondary to changes in albumin (% changes Pearson correlation=0.68, P<0.0001). No difference in the rate of proteinuria was observed across FG and G arms of the 6162 trial.

    Conclusion
    Decrease in SA during ficlatuzumab treatment was seen in almost all patients and appears to be unrelated to hepatotoxicity. Decrease in SA resulting from ficlatuzumab treatment may be the cause of peripheral edema. Both hypoalbuminemia and peripheral edema were frequently observed with other HGF/c-Met inhibitors, suggesting they may be class adverse events. Decrease in SA could be explored as a PD marker for HGF/c-Met inhibition.