Assessment of Treatment with Visible Light Activated Synthetic Hypericin ointment in Mycosis Fungoides Patients.

7. Project Summary/Abstract Mycosis Fungoides/Cutaneous T Cell Lymphoma (MF/CTCL) is a rare, indolent Non-Hodgkin's Lymphoma (NHL), without a known cure, that presents as skin patches, plaques, tumors, or erythroderma with significant morbidity and impact on health-related quality of life (HR-QoL). Effective early treatment improves HR-QoL and may prevent disease progression. As per current NCCN guidelines, many skin-directed therapies (SDTs) are used for the treatment of early stage MF/CTCL including topicals, ultraviolet (UV) phototherapy, and radiation therapy. None have been FDA-approved for first-line therapy and most are used off-label. Given the chronic, recurrent nature of MF/CTCL, most patients require repeat courses of therapy and trying other therapies. The use of several SDTs are limited by skin irritation/dermatitis and long-term cumulative toxicity. Given this, there is an urgent need for additional SDTs for CTCL with fewer side effects. Topical hypericin is non-mutagenic, not systemically absorbed, activated by noncarcinogenic visible light, selectively taken up by tumor cells in the skin (up to 10-fold) and induces mitochondrial apoptosis. Phase 1, 2 and 3 clinical studies in MF/CTCL have demonstrated safety and efficacy. A recent multicenter, randomized, placebo-controlled, blinded Phase 3 study, enrolled 169 patients with Stage IA, IB or IIA CTCL and administered treatments twice weekly for at least 6 weeks (Cycle 1). In Cycle 1, 116 subjects received SGX301 to 3 index lesions with an overall response rate (ORR) of 16% compared to placebo ORR 4% (n=50, p=0.04). In Cycle 2 the ORR in patients receiving SGX301 for both cycles (12 weeks) was 40% (p<0.0001 vs placebo or 6 weeks of treatment). SGX301 treatment is safe and well tolerated, with potential favorable long-term safety given its mode of action. Although the trial showed efficacy, the dosing regimen was inflexible and short duration vs other skin-directed therapies where peak ORR can take 4-24 months of treatment. The current proposal will study SGX301 efficacy/safety utilizing a continuous treatment schedule for up to 1 year in an open label, multicenter clinical trial of 50 patients over 6 sites. The Specific Aims are: 1: Define optimal duration of SGX301 therapy to maximal ORR in early stage MF/CTCL patients on a “real world” treatment schedule up to 12 months. 2: Define safety profile during treatment. 3: Assess efficacy of SGX301 in disease subtypes and different skin lesions (patch vs plaque). 4: Assess genomic changes in skin/peripheral blood (utilizing high throughput sequencing [HTS-PCR] and targeted next generation sequencing [NGS]) and apoptosis markers (utilizing immunohistochemistry) as correlates of clinical response to SGX301 therapy.