Cutaneous Squamous Cell Carcinoma

The Clinical Need

Non-melanoma skin cancer is the most common malignancy affecting caucasian populations. Approximately 75-80% of cases are basal cell carcinomas (BCC), and 20-25% are squamous cell carcinomas (SCC).   The predominant cause of non-melanoma skin cancers (NMSC) is UV exposure, although a small proportion of cases are related to prior environmental exposures such as psoralens treatment and very rare genetic conditions such as Xeroderma Pigmentosum (principally SCC) and Gorlin syndrome (BCC). Immune suppression is also an important cause of difficult to treat SCC with a high relapse risk.

The incidence of these cancers has been rising steadily in Europe, North America, Australia and New Zealand.  Australia has one of the highest incidences in the world. This rise in incidence reflects population aging and increased UV exposure.  The risk of developing cutaneous SCC is approximately 10% in a lifetime. The vast majority are treated surgically and without recurrence but a percentage do become locally advanced and difficult to treat.  This is usually due to late presentation,  difficult anatomical sites or patient co-morbidities that can preclude aggressive therapy. Many locally advanced NMSC can arise on the face, ears, head and forearms and the surgical excision of such lesions may result in functional impairment and cosmetic disfigurement.  For the advance SCC patient, systemic chemotherapies can be used as palliative care but are associated with significant side effects and are not curative.

Rationale

Ascend is developing ASN-002 in combination with chemotherapy to be administered intra-lesionally into cutaneous SCCs.  ASN-002 is based on a replication deficient adenovirus type 5 engineered to express IFNγ – a potent protein that can stimulate the immune system to destroy cancers.   Previous clinical trials by independent groups have demonstrated the utility of recombinant Interferon-γ in head and neck SCC patients.  In recent preclinical studies, the combination of ASN-002 plus select chemotherapy agents could trigger multiple forms of regulated cell death and was superior to ASN-002 alone.  The combination treatment will be evaluated in SCC patients with recurrent disease that is chemotherapy resistant.