Perlmutter Cancer Center

Although recent advances have been made in the treatment of some solid tumors, there remains a high unmet need for patients who have malignancies that have relapsed or are refractory to chemotherapy, including targeted therapies, immunotherapy, or radiotherapy. OV therapy utilizes engineered viral particles (VPs) to directly lyse tumor cells and increase the amount of tumor antigen able to be processed and presented to the immune system. Thus far, only one approved OV therapy exists in the US. Imlygic® (talimogene laherparepvec) (Imlygic® USPI) is a herpes simplex virus 1 coding for granulocyte macrophage colony-stimulating factor (GM-CSF) and is approved for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Imlygic® has not been shown to have an effect on visceral metastases. In a recent phase 3 randomized, double-blind trial, MASTERKEY-265, Imlygic and pembrolizumab did not show increased progression free survival or overall survival over placebo and pembrolizumab for patients with melanoma. No OV options exist for other solid tumors, including lung, breast, colon, genitourinary, and central nervous system, or as IV administration as systemic therapy. Despite these data, OV therapy represents a unique type of therapy that combines self-amplification and self-propagation, as well as lytic and immunostimulatory properties against cancer. Very little progress has been made in the treatment of solid tumor where chemotherapy and checkpoint inhibitors are the mainstay of treatment for metastatic disease. These are limited by eventual resistance and toxicity. Viral agents may represent an alternative approach to target tumor specific cells while sparing normal cells. OVs remain a promising approach as virus can infect tumor cells and selectively replicate in them, leading to cancer cell lysis, and release of new viruses, which can infect additional tumor cells. Furthermore, virus could spread to distant ICVB-1042 Clinical Study Protocol 1042-CLN01 V2.0 Confidential 20 IconOvir Bio tumor metastasis and induce a systemic immune system to react against the tumor. When the tumor is eradicated, the virus is unable to further replicate and it thus cannot exist. Study 1042-CLN01 is a Phase 1 first-in-human (FIH) dose escalation and expansion study to assess safety and tolerability of IV administration of ICVB-1042 in patients with advanced or metastatic solid tumors that have relapsed and/or are refractory to at least one prior line of standard treatment, or the patient is not able to tolerate available therapies, or such therapies are contraindicated. Patients who have refused standard treatments may be eligible for this study after discussion with the sponsor/medical monitor.