Anti-mesothelin vaccine CRS-207 with or without low-dose cyclophosphamide plus chemotherapy as front-line treatment for malignant pleural mesothelioma (MPM)

  • Raffit Hassan
  • Evan Alley
  • Hedy Kindler
  • Scott Antonia
  • Thierry Jahan
  • Anish Thomas
  • Somayeh Honarmand
  • Aimee L Murphy
  • John J Grous
  • Dirk G Brockstedt
Open Access
Poster presentation

Keywords

Listeria Pemetrexed Listeria Monocytogenes Malignant Pleural Mesothelioma Good Performance Status 

Background

CRS-207 is live-attenuated, double-deleted Listeria monocytogenes (LADD) engineered to express the tumor-associated antigen mesothelin which is highly expressed in malignant pleural mesothelioma (MPM). CRS-207 stimulates potent innate and adaptive immunity and in combination with chemotherapy may act synergistically to alter the tumor environment to be more susceptible to immune-mediated killing. Preliminary data of 32 patients who received CRS-207 in combination with pemetrexed/cisplatin showed 60% partial responses and 94% disease control[1]. Low-dose cyclophosphamide (Cy) in combination with LADD improved immune and anti-tumor responses and overall survival in preclinical studies.

Methods

Up to 60 subjects are planned to be enrolled in 2 mutually exclusive, sequential cohorts at 5 clinical trial sites. Patients must be chemotherapy-naïve, have unresectable MPM, good performance status (ECOG 0 or 1) and adequate organ function. Eligible patients in Cohort 1 receive 2 prime vaccinations with CRS-207 (1 × 109 CFU; 250 mL IV over 2 hours) 2 weeks apart, followed by up to 6 cycles of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) 3 weeks apart and 2 CRS-207 boost vaccinations 3 weeks apart. Subjects are followed every 8 weeks until disease progression. Clinically stable patients continue CRS-207 maintenance vaccinations every 8 weeks. Patients in Cohort 2 receive low-dose Cy (200 mg/m2) 1 day prior to each CRS-207 vaccination. Objectives of the study are safety, immunogenicity, objective tumor responses and tumor marker kinetics.

References

  1. 1.
    Hassan , Antonia , Alley , et al: Mesothelin-targeted immunotherapy CRS-207 in combination with standard of care chemotherapy as treatment for malignant pleural mesothelioma (MPM). J Clin Oncol. 2015, 33 (suppl): abstr 7565Google Scholar

Copyright information

© Hassan et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • Raffit Hassan
    • 1
  • Evan Alley
    • 2
  • Hedy Kindler
    • 3
  • Scott Antonia
    • 4
  • Thierry Jahan
    • 5
  • Anish Thomas
    • 1
  • Somayeh Honarmand
    • 6
  • Aimee L Murphy
    • 6
  • John J Grous
    • 7
  • Dirk G Brockstedt
    • 6
  1. 1.Center for Cancer Research at the National Institutes of HealthBethesdaUSA
  2. 2.University of PennsylvaniaPhiladelphiaUSA
  3. 3.The University of Chicago MedicineChicagoUSA
  4. 4.H. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  5. 5.University of California San FranciscoSan FranciscoUSA
  6. 6.Aduro Biotech Inc.BerkeleyUSA
  7. 7.Aduro Biotech Inc.HopedaleUSA

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