Author of

• 25943

  +

  P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 27020

    +

    P2.06-11 - A Phase I/II Study of Intrapleural Ad-SGE-REIC Administration in Patients with Refractory Malignant Pleural Mesothelioma (ID 11328)

    16:45 - 18:00  |  Author(s): Hiromi Kumon
    • Abstract

    Background
    

    Reduced expression in immortalized cell (REIC)/Dickkopf-3 (Dkk-3) is a tumor-suppressor gene and REIC/Dkk-3 expression was markedly downregulated in various human cancer cells. REIC/Dkk-3 protein is also known as a key player, namely an antagonist of the Wnt signaling pathway. Ad-SGE-REIC is an adenoviral vector carrying REIC/Dkk-3 that mediates cancer cell death induction and anti-cancer immunity augmentation.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We conducted a phase I/II, 3+3 design, dose escalation study in malignant pleural mesothelioma (MPM) patients (pts) with measurable lesions. Pts with refractory to or unsuitable for standard chemotherapy received 2 intrapleural administrations of Ad-SGE-REIC on days1 and 4. Three escalating doses of level (DL) 1: 3.0×10¹¹, DL2: 1.0×10¹² and DL3: 3.0×10¹² viral particles were employed. This dosage and regimen were set by considering the reason of manufacturing and neutralizing anti-body for adenovirus. The safety and dose-limiting toxicities (DLTs) of Ad-SGE-REIC were evaluated for 32 days. Continuous safety and efficacy were assessed for 172 days using modified RECIST (mRECIST). The concentrations of REIC/Dkk-3 in pleural fluid also were measured as indirect indication of targeted gene expressions.

    4c3880bb027f159e801041b1021e88e8 Result
    

    From 07/2015 to 09/2017, a total of 13 pts have been treated at DL1 (n=4 included one fatal case within 32 days), DL2 (n=3) and DL3 (n=6). Male: 100%; median age 70; PS 0: 23%, 1: 69%, 2: 8%; epithelial/biphasic histology: 69%/15%; Stage III-IV: 77%; previous chemotherapy use with platinum-pemetrexed: 92%. Treatment-related AEs (TRAEs) were all Grade 1-2 and no DLTs occurred. The most frequent TRAEs were fever and CRP increase based on adenovirus infection. Tumor responses assessed by independent central review showed that there was no objective response and DCR was 62% (8/13 pts). Median PFS was 3.4 months at all groups and 5.7 months at DL3. A remarkable increase of REIC/Dkk-3 concentration in pleural fluid was determined (6/13 pts, prominently high in DL3).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    The intrapleural administration of Ad-SGE-REIC up to 2 cycles was safe and well tolerated in MPM pts and promising results of efficient REIC/Dkk-3 expression and durable disease control were obtained. We are planning phase II study using repeated intrapleural or intratumoral administration.

    6f8b794f3246b0c1e1780bb4d4d5dc53