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A phase II study of REOLYSIN® (pelareorep) in combination with carboplatin and paclitaxel for patients with advanced malignant melanoma

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Abstract

REOLYSIN® (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN® on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN®. Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile. The current study is a phase II, single-arm, open label trial of REOLYSIN® in combination with carboplatin and paclitaxel for patients with advanced melanoma. Results from the 14 patients enrolled in the study exhibited no grade 4 adverse events or deaths but manageable grade-3 toxicities commonly attributed to REOLYSIN®, including pyrexia, chills, myalgia, pain, fatigue, and nausea. The number of treatment cycles ranged from 2 to 20 with a median of 6 cycles. The study met its treatment and efficacy goal for the first stage with three partial responses (ORR was 21%). No complete responses were noted. The median PFS and OS were 5.2 and 10.9 months, respectively. The 1-year OS was 43% with a disease control rate of 85%. In conclusion, REOLYSIN® combined with carboplatin and paclitaxel is a safe and potentially efficacious therapy for patients with advanced malignant melanoma. Additional combination studies using REOLYSIN® with chemo/immunotherapy drugs may support more favorable outcomes for patients in this indication.

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Acknowledgements

Devalingam Mahalingam (first author) and the sponsor (Oncolytics Biotech Inc.) designed the study. The sponsor also covered all study-related expenses and provided REOLYSIN® free of charge. Christos Fountzilas is a recipient of a Cancer Research Training Award from the Cancer Prevention and Research Institute of Texas (RP140105).

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Authors and Affiliations

  1. Division of Hematology/Oncology, Cancer Therapy and Research Center, University of Texas Health Science Center, 7979 Wurzbach Rd, San Antonio, TX, 78229, USA

    Devalingam Mahalingam, Christos Fountzilas, Jennifer Moseley & John Sarantopoulos

  2. Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, San Antonio, TX, USA

    Devalingam Mahalingam, Jennifer Moseley & John Sarantopoulos

  3. Oncolytics Biotech Inc., 210, 1167 Kensington Cr. NW, Calgary, AB, Canada

    Nicole Noronha, Hue Tran, Romit Chakrabarty, Giovanni Selvaggi, Matthew Coffey & Brad Thompson

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  1. Devalingam Mahalingam
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Corresponding author

Correspondence to Devalingam Mahalingam.

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Funding

This study was funded by Oncolytics Inc (study sponsor).

Conflict of interest

Devalingam Mahalingam declares that he has no conflict of interest. Christos Fountzilas declares that he has no conflict of interest. Jennifer Moseley declares that she has no conflict of interest. John Sarantopoulos declares that he has no conflict of interest. Nicole Noronha, Hue Tran, Romit Chakrabarty, Matt Coffey, and Brad Thompson are employed by Oncolytics Biotech Inc., with stock options and/or stock. Giovanni Selvaggi was employed with Oncolytics Biotech Inc. during a portion of this study and manuscript preparation.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Mahalingam, D., Fountzilas, C., Moseley, J. et al. A phase II study of REOLYSIN® (pelareorep) in combination with carboplatin and paclitaxel for patients with advanced malignant melanoma. Cancer Chemother Pharmacol 79, 697–703 (2017). https://doi.org/10.1007/s00280-017-3260-6

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  • DOI: https://doi.org/10.1007/s00280-017-3260-6

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