Vienna Conference Looks Promising

VLA will be presenting at the European Cancer Conference in Vienna on 26 September. A copy of VLA's poster presentation - Abstract No. 510 -  is noted below (emphasis is mine.)

The report describes that Cavatak was used in mouse models with immune-checkpoint blockade CTLA-4-mAbs (most likely Yervoy) and PD-1 (most likely Keytruda or Optivo). The result was that the combination with Cavatak offered significantly greater survival benefits than when compared with either of the drugs used alone.

With Yervoy, Keytruda and Optivo each having achieved or about to achieve billion dollar a year sales, the chance to obtain significantly greater efficacy in combination with Cavatak must be a massive attraction. We know Cavatak is being trialled with Yervoy and that prelim results will be provided in the first quarter next year. VLA hasn't yet indicated if they are also working with Keytruda and Optivo, but you'd think it highly likely.

My guess is that when (if) T-Vec  gains formal FDA approval late next month, there will be no clinical restriction on Cavatak being quickly accepted for use on humans.  We just need Bristol Myers Squibb, Merck, Johnson and Johnson or Roche to do a deal.

Immune-checkpoint blockade in combination with a novel oncolytic immunotherapeutic agent, Coxsackievirus A21, significantly reduces tumor growth and tumor rechallenge

1. Quay, Y. Wong, G. Au, D. Shafren

Background: Coxsackievirus A21 (CAVATAK™) is a bio-selected oncolytic immunotherapy virus. Following intravenous (i.v) infusion, CVA21 preferentially infects ICAM-1 expressing tumor cells, resulting in tumor cell lysis and a potential systemic immune-mediated anti-tumor response. A Phase I/II trial of i.v delivered CVA21 (NCT01227551) in advanced cancer patients has displayed preliminary signs of anti-tumor activity in some lesions associated with increased levels of viral challenge. Blockade of programmed death protein-1 (PD-1) and or CTLA-4 in patients with advanced solid tumors has resulted in substantial tumor responses via a mechanism involving reversal of tumor induced T-cell suppression. We hypothesized that combinations of intravenous delivered CVA21 and PD-1 or CTLA-4 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 CVA21 and anti-mouse PD-1 (mPD-1) mAb or anti-CTLA-4 (mCTLA-4) mAb 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 CVA21 binding and cell infection. CVA21 was administered i.v, while anti mPD-1 or mCTLA-4 mAbs were delivered via the intraperitoneal (i.p) route. Following challenge of the primary cutaneous B16-ICAM-1 tumor with 4 cycles of i.v CVA21 and 4 cycles of i.p anti-PD-1 or anti-CTLA-4 mAbs, mice were then re-challenged with an additional subcutaneous administration of B16 cells.
Results: Significant single agent anti-tumor activities against the primary B16-ICAM-1 tumors were observed in mice treated with either i.v CVA21, i.p anti-PD-1 or anti-CTLA-4 mAbs relative to saline controls. Furthermore, combinations of i.v CVA21 and i.p anti-PD-1 or anti-CTLA-4 mAbs, mediated significantly greater anti-tumor activity and offered greater survival benefits when compared to use of either agent alone. Of particular interest was the finding that combinations of CVA21 and anti-PD-1 or anti-CTLA-4 mAbs were able to noticeably delay the onset of palpable tumor development following B16 cell re-challenge when compared to all other single agent treatment regimes.
Conclusion: The significant anti-tumor activity mediated by the combination of i.v CVA21 and i.p checkpoint inhibitor antibodies (anti-PD-1 and anti-CTLA-4) observed in the presented murine melanoma model supports clinical evaluation of such an immunotherapeutic combination treatment regime in patients with advanced solid malignancies. Clinical evaluation of CVA21 in combination with immune checkpoint blockade in advanced melanoma patients is currently underway

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