SGX301 for cutaneous T-cell lymphoma | Positive results from phase III FLASH study

The phase III Fluorescent Light Activated Synthetic Hypericin (FLASH) study is comparing SGX301, to placebo, in patients with early-stage cutaneous T-cell lymphoma (CTCL). On March 19, 2020, positive topline results from the trial were announced with SGX301 leading to a significantly improved treatment response compared with placebo after six weeks of treatment.¹ Subsequently, on April 30, 2020, it was announced that SGX301 continued to significantly improve responses after 12 weeks of therapy compared with placebo.²

SGX301¹

SGX301 is a first-in-class photodynamic therapy that is activated by safe visible light. It is formed of 0.25% synthetic hypericin which is a potent photosensitizer that is applied topically to skin lesions and is subsequently activated by fluorescent light 16–24 hours later.

SGX301 has been granted orphan drug designation and fast track designation by the U.S. Food and Drug Administration (FDA) and orphan drug designation by the European Medicines Agency (EMA).

FLASH study¹

• Patients with stage IA, IB or IIA CTCL were enrolled (n= 169) and randomized 2:1 to receive SGX301 or placebo twice weekly for the first six weeks of an eight-week cycle
• In total, there were three treatment cycles of eight weeks:
  • Cycle 1 (double-blind): patients randomized to SGX301 vs placebo for index lesions
  • Cycle 2 (open-label): all patients received SGX301 for index lesions
  • Cycle 3 (open-label): optional continuation of SGX301 for all lesions
• The primary endpoint was the percentage of patients in each arm achieving a partial or complete response of treated lesions defined as a ≥50% reduction in the total Composite Assessment of Index Lesion Severity (CAILS) score for three index lesions at the eight-week assessment at the end of Cycle 1
• Results from the first double-blind treatment cycle are shown in Table 1 demonstrating that SGX301 led to a statistically significant improvement in treatment responses (p = 0.04) compared with placebo
• SGX301 was also found to be well-tolerated

Table 1. Results from the first double-blind treatment cycle¹

	SGX301 n = 116	Placebo n = 50	p value
≥ 50% reduction in index lesions using CAILS score at 8 weeks, %	16	4	0.04
CAILS, Composite Assessment of Index Lesion Severity

 

Updated results²

In Cycle 2, all patients received SGX301, meaning data are available for patients receiving six weeks of placebo followed by six weeks of SGX301 (n = 45) and patients who continued SGX301 for a total of 12 weeks (n = 110).²

• In patients who received SGX301 twice weekly for 12 weeks, the response rate was 40%
• This was significantly higher than the response to placebo treatment in Cycle 1, p < 0.0001
• Additionally, the response rate was significantly higher in patients receiving 12 weeks of treatment compared with six weeks of treatment, p < 0.0001
  • SGX301 appears to induce better outcomes with longer treatment duration
• Consistent with the results from Cycle 1, SGX301 continued to be safe and well-tolerated

CTCL

CTCL is a form of non-Hodgkin lymphoma (NHL) involving the expansion of malignant T-cell lymphocytes that migrate to the skin and cause lesions. The Lymphoma Hub is focusing on T-cell lymphomas as a new Educational Theme.