Phase I STORM study (KEYNOTE 200): Intravenous delivery of a novel oncolytic immunotherapy agent, Coxsackievirus A21 in combination with pembrolizumab in advanced cancer patients.

Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors

“…Generally, systemic delivery of CVA21 appeared well tolerated and able to reach metastatic sites. [330][331][332] The latter observation is encouraging for a synergistic effect with pembrolizumab considering the ability of CVA21 tumor infection to restore immune cell infiltration and upregulate the expression of immune checkpoint molecules. 334 Finally, the Phase I/II CANON trial (NCT02316171) is investigating the safety and efficacy of escalating doses of neoadjuvant CVA21, delivered i. v. in 16 first-line patients with bladder cancer, either alone or in combination with low-dose mitomycin C. 333 Observations indicate general tolerance of i.v.…”

“…(1) CAVATAK (Viralytics, Sydney, Australia), a proprietary formulation of the common cold coxsackievirus type A21 (CVA21), is being investigated against advanced malignancies in several clinical studies. [330][331][332][333][334] The completed Phase II CALM trial (NCT01227551) demonstrated the tolerability and efficacy of intralesional CVA21 monotherapy in 57 patients affected by late-stage melanoma. 334,335 The ORR assessed by irRECIST was 28.1% with a ≥ 6 months durable response rate (DRR) of 21.1%.…”

“…334 Along this line, the Phase Ib STORM trial (NCT02043665) was designed to evaluate the safety and efficacy of CVA21 administered systemically either as a standalone therapy (part A, n = 16) or in combination with the anti-PD-1 pembrolizumab (part B, still recruiting) against late-stage solid tumors. [330][331][332] Each arm includes 3 cohorts in a dose escalation design. In part A, no severe AEs were observed.…”

Oncolytic immunotherapy: unlocking the potential of viruses to help target cancer

“…Of these 48% had a confirmed response, and 14% had a confirmed CR [ 78 ]. Additional combination studies include the phase 1 STORM (KEYNOTE 200) study, which is evaluating the safety and efficacy of CVA21 in combination with pembrolizumab in patients with non–small-cell lung cancer and bladder cancer [ 79 ] and PHOCUS, the randomized phase 3 study of pexastimogene devacirepvec, followed by sorafenib versus sorafenib alone in patients with hepatocellular carcinoma [ 80 ]. Both studies are currently recruiting participants, with results expected in 2019 and 2017, respectively.…”