1066P - Combination of a novel oncolytic immunotherapeutic agent, coxsackievirus A21 and PD-1 blockade significantly reduces tumor growth and improves surv...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Basic Science
Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Presenter Darren Shafren
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors D. Shafren1, M. Quah2, Y. Wong2, R.H. Andtbacka3, G. Au2
  • 1Oncology, Viralytics,, 2300 - Sydney/AU
  • 2School Of Biomedical Science And Pharmacy, The University of Newcastle, 2300 - Newcastle/AU
  • 3Surgical Oncology, Huntsman Cancer Institute, Salt lake City/US

Abstract

Aim

Coxsackievirus A21 (CAVATAKTM) is a bio-selected oncolytic immunotherapy virus. Following intratumoral (i.t) injection, CAVATAK preferential infects ICAM-1 expressing tumor cells, resulting in tumor cell lysis and a systemic immune-mediated anti-tumor response. A Phase II trial of i.t delivered CAVATAK in advanced melanoma patients has highlighted antitumor activity in both injected and distant non-injected lesions. Blockade of programmed death receptor-1 (PD-1) in patients with metastatic melanoma has resulted in substantial tumor responses via a mechanism involving reversal of tumor induced T cell suppression. We hypothesized that combination of CAVATAK and PD-1 blockade may enhance antitumor responses, potentially leading to improved clinical activity.

Methods

Preclinical studies in C57BL mice were conducted to assess the antitumor activity of CAVATAK and anti-mouse PD-1 (mPD-1) mAb (2A3-IgG2a) in a B16-ICAM-1 melanoma immune competent mouse model. B16-ICAM-1 cells are murine melanoma B16 cells stably transfected to express human ICAM-1 allowing CAVATAK binding and cell infection. CAVATAK (∼108TCID50) was administered i.t, while anti mPD-1 mAb (12.5 mg/kg) was delivered via the intraperitoneal route. Following treatment of the primary cutaneous B16-ICAM-1 tumor with 8 cycles of CAVATAK injections and 4 cycles of anti-PD-1mAb, mice were then challenged with an additional subcutaneous administration of B16 cells.

Results

Significant single agent antitumor activities against the primary B16-ICAM-1 tumor were observed in mice treated with either CAVATAK or anti-PD-1 mAb relative to saline controls. Furthermore, combination of CAVATAK and anti-PD-1 mAb mediated significantly greater antitumor activity and offered greater survival benefit when compared to use of either agent alone. Of particular interest was the finding that a combination of CAVATAK and anti-PD-1 mAb was able to noticeably delay the onset of palpable tumor development following B16 cell challenge when compared to all other single agent treatment regimes.

Conclusions

The significant anti-tumor activity mediated by the combination of CAVATAK and anti-PD-1 mAb blockade observed in the presented murine melanoma model supports clinical evaluation of such an immunotherapeutic combination treatment regime in patients with advanced melanoma.

Disclosure

D. Shafren: Author is CSO of Viralytics and holds stock; M. Quah and Y. Wong: Receives research support from Viralytics; R.H. Andtbacka: has received travel support from Viralytics; G. Au: Receives research support from Viralytics and holds stock