Author of

• 10801

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  P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10820

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    P1.11-019 - Phase 2 double-blind, placebo-controlled study of three-weekly farletuzumab with a platinum containing doublet in subjects with previously untreated folate receptor alpha (FRA) expressing non-small-cell lung cancer (NSCLC) (ID 1616)

    09:30 - 09:30  |  Author(s): D.J. O'Shannessy
    • Abstract

    Background
    Farletuzumab (FAR) is a humanized monoclonal antibody that binds to folate receptor alpha, which is highly expressed in NSCLC, specifically adenocarcinoma. FAR potentially has anti-tumor activity via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, and was studied in a Phase 2 NSCLC trial.

    Methods
    This was a global, double-blind, randomized Phase 2 trial in 130 patients with previously untreated FRA-expressing NSCLC. Patient tumors were screened using a FRA immunohistochemical diagnostic assay at a central pathology lab. Subjects could receive carboplatin and paclitaxel, carboplatin and pemetrexed, or cisplatin and pemetrexed for 4 to 6 cycles combined with randomized test product (FAR 7.5 mg/kg every three weeks with chemotherapy, or placebo). Cycle 1 included a loading dose on Day 1 of Week 2. Single agent test product was then continued every three weeks until disease progression. The primary endpoint was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors, 1.1.

    Results
    One hundred and thirty patients were randomized. All had adenocarcinoma with one patient having a mixed adeno-squamous histology. All subjects had some expression of FRA in their tumor tissue as assessed by IHC. Median PFS as determined by primary investigator was 5.9 (placebo) and 4.7 (FAR) months with no statistically significant difference between arms (HR=1.22 [95% CI: 0.78, 1.89]). PFS as assessed by an independent evaluator showed a median PFS of 5.9 (placebo) and 6.7 (FAR) months with a HR of 0.91 (95% CI: 0.54, 1.51). The most commonly reported adverse events across arms were those known to be associated with chemotherapy such as hematologic toxicities occurring during combination therapy phase of the study. Preliminary analysis showed that subjects whose serum farletuzumab concentration level was in the top quartile did not reach a median PFS compared to those on placebo. Further investigation is currently on-going.

    Conclusion
    The study did not meet its primary PFS endpoint. The secondary end point of OS was immature at the time of this analysis. The most commonly reported adverse events across arms were those known to be associated with the study chemotherapy agents. Preliminary pharmacokinetic / pharmacodynamic analysis identified patients with a high serum concentration of FAR that may have benefited from treatment.