Author of

• 10883

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  P1.14 - Poster Session 1 - Mesothelioma (ID 194)

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

  • 10888

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    P1.14-005 - Preliminary Results - "A Phase I Trial of Oncolytic Measles Virotherapy in Mesothelioma" Investigating the Intrapleural Administration of the Modified Vaccine Strain Measles Virus (MV-NIS) to Patients with Malignant Pleural Mesothelioma (ID 1922)

    09:30 - 09:30  |  Author(s): E. Galanis
    • Abstract

    Background
    Malignant pleural mesothelioma (MPM) remains an almost universally fatal disease. Preclinical models indicate that the oncolytic modified vaccine strain measles virus (MV) carrying the gene for the human sodium-iodine symporter (NIS) - MV-NIS preferentially targets MPM tumors cell. In patients with refractory ovarian cancer the intraperitonial administration of MV-NIS was recently found to be safe and induced an anti-tumor immune response.

    Methods
    Phase I dose escalation study (3+3 design). MV-NIS is administered intrapleurally. Starting dose level was 10[8] TICID 50 (Level 1) and the current dose level is 3 x 10[8] TICID 50 (Level 2). In the absence of dose limiting toxicity and disease progression patients continue MV-NIS therapy for up to six 28-day cycles. MV-NIS infection and replication is monitored by Iodine[123] SPECT/CT and RT-PCR and anti-tumor and anti-viral immunity are monitored in correlative studies. Patients are followed clinically using modified RECIST criteria.

    Results
    Up to now 4 patients have received MV-NIS therapy. Three patients were treated at Level 1 and the fourth patient at Level 2. No dose limiting adverse events occurred. The best therapeutic response was stable disease, observed in patient #1 for 6 months and patient #2 for 2 months. The remaining two patients progressed radiologically after one treatment cycle. I[123] SPECT-CT imaging did not demonstrate changes in iodine uptake compared to baseline in any of these patients. However, we detected MV RNA by QRT-PCR within the pleural cells 24-48 hours after the intrapleural administration of MV-NIS in 3/4 patients. In patient #4, treated with 3x10[8] TCID 50, MV replication was detectable within the pleural space by plaque assay 24 hours after MV-NIS administration. Following MV-NIS therapy a profound influx of neutrophils into the pleural space occurred in 3/4 patients and pleural fluid cytokine concentrations changed significantly. In addition, a humoral anti-tumor immune response emerged in patients #2.

    Patient #	Age	Disease Stage	Histology	Line therapy
    1	75	II (T2N0M0)	Epitheloid	First
    2	53	IV (T4N0M0)	Epitheloid	Second
    3	84	IV (T4N0M0)	Epitheloid	First
    4	73	IV (T2N3M0)	Mixed	First

    Conclusion
    Thus far the intrapleural administration of MV-NIS appears to be safe and well tolerated in MPM. Our study will continue to enroll patients.