ASCO 2016: CAVATAK (intralesional treatment derived from the Coxsackievirus) Factors that improve response!

I recently posted this:  CAVATAK Intralesional therapy for melanoma

Here's what was posted at ASCO regarding factors that improved response....

Dynamics of tumor response in advanced melanoma patients treated with Coxsackievirus A21.  ASCO 2016. #9553.  J Clin Oncol 2016.  Andtbacka, Curti, Kaufman, et al.

Background: CAVATAK, an oncolytic immunotherapy, is a bio-selected oncolytic strain of Coxsackievirus A21 (CVA21). Intratumoral (IT) injection of CVA21 induces lytic tumor cell infection, up-regulation of immune checkpoint molecules and increased immune-cell infiltration. The Phase II CALM study investigated the efficacy and safety of IT CVA21 in 57 pts with advanced melanoma resulting in a confirmed ORR of 28.1% and DRR of 21.1%. The CALM extension study (13 pts) investigated CVA21 induced changes in immune cell infiltrates within the tumor-microenvironment (TME). We describe factors regarding the nature of clinical responses in 70 pts with stage IIIC-IV melanoma given IT CVA21. Methods: The association of prior lines of therapy, tumor pseudo-progression, baseline tumor burden (BTB) and levels of immune cell infiltrates in the TME were examined with regard to clinical response. Results: Responders on the CALM study (16/57 pts, 28.1%) displayed reductions in both injected and non-injected lesions, suggesting the generation of significant host anti-tumor responses. A comparable ORR was observed in pts administered prior immunotherapy, 29.0% (9/31) vs other tx 27.0% (7/26). Interestingly, 26.7% (4/15) and 40% (2/5) of pts previously treated with ipilimumab and talimogene laherparepvec, respectively, developed confirmed responses. Three pts (18.8%) exhibited pseudo-progression (irRECIST criteria) prior to response. BTB of the 57 pts in the CALM study was 3.9 cm. A BTB less than median was associated with: superior ORR (39.3 vs 17.2 %), superior DRR (35.7 vs 6.9 %), and greater OS. In the CALM extension study, CVA21 tx induced increases in immune cell infiltrates within the TME. In patients with responses, increases in CD8⁺ T-cells and PD-L1⁺ expression were observed in injected lesions. Reconstitution of immune cell infiltrates was observed in a number of CVA21 treated lesions from pts failing prior tx with immune-checkpoint blockade. Conclusions: IT administration of CVA21 can notably influence the dynamics of the TME and generate systemic anti-tumor immune responses as evidenced by increases in immune cell infiltrates and widespread non-injected lesion responses. Clinical trial information: NCT01227551

These are small numbers, but...CAVATAK certainly changed the tumor-microenvironment, worked in treated and UN-treated lesions, previous treatment with ipi or T-VEC may make it work better, and as would be expected, folks with a lower tumor burden did better.  Pseudoprogression was also noted at times.

It seems reasonable to assume that combining CAVATAK with a systemic therapy (as noted in the prior post) should improve responses! -c