Author of

• 11826

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  P2.14 - Poster Session 2 - Mesothelioma (ID 196)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Mesothelioma
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11838

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    P2.14-012 - Oncolytic herpes virus therapy for mesothelioma- a Phase I study of intrapleural oncolytic virus HSV1716 (NCT01721018) (ID 1627)

    09:30 - 09:30  |  Author(s): P. Woll
    • Abstract

    Background
    Malignant pleural mesothelioma (MPM) remains a major challenge, with limited therapeutic options. Multifocal intrapleural disease can cause disabling symptoms of pain and breathlessness in the absence of distant metastases, so an intrapleural treatment approach is attractive. HSV1716 is a mutant herpes simplex virus type 1 deleted in the RL1 gene which encodes the protein ICP34.5, a specific determinant of virulence. Mutants lacking the RL1 gene are capable of replication in actively dividing cells but not in terminally differentiated cells – a phenotype exploited to selectively kill tumor cells. Activity against mesothelioma has been demonstrated in animal models. Studies in adult patients with high grade glioma, melanoma and squamous cell carcinoma report that HSV1716 is safe and well tolerated when administered by intra-tumoral injection. We have therefore designed a phase I study to determine the safety, tolerability and potential for efficacy of HSV1716 given intrapleurally to patients with MPM.

    Methods
    The study is an open label, dose escalation, phase I/IIa study in a single clinical centre. Patients with a histological diagnosis of MPM and an indwelling pleural catheter are eligible if they have performance status ≤ 2 and adequate hematologic, renal and liver function. Patients will receive 1x10[7]iu HSV1716 through their pleural catheter on one, two or four occasions a week apart, in three separate patient cohorts. The primary objectives are to determine the safety and tolerability of HSV1716 given intrapleurally in patients with inoperable MPM. Detailed safety analyses will be undertaken. The secondary objective is to obtain evidence of HSV1716 replication and lysis of mesothelioma cells through analysis of pleural fluid by determining the number of viral particles on alternate days for one week, after the last Seprehvir administration, then weekly. An exploratory objective will be to assess tumour response by CT using modified RECIST criteria.

    Results
    The study is open and the first two patients have been treated with a single dose of HSV1716 with no dose limiting toxicity (DLT) or serious adverse events (SAEs) reported. HSV1716 DNA has been detected in pleural fluid samples from one of the patients up to one month post treatment.Up to 12 patients will be recruited and, if successful, a randomised phase II study of intrapleural HSV1716 is planned.

    Conclusion
    Not applicable.