A data monitoring committee recommended halting the phase 3 FLASH2 trial investigating HyBryte in CTCL due to futility.
A data monitoring committee (DMC) has recommended halting the phase 3 FLASH2 trial (NCT06470451) due to futility following an interim efficacy analysis.1 The trial is evaluating synthetic hypericin (HyBryte) for the treatment of patients with cutaneous T-cell lymphoma (CTCL).1,2
FLASH2 was designed as a confirmatory study for the evaluation of HyBryte in patients with CTCL following positive data from the phase 3 FLASH trial (NCT02448381).1,3 In February 2023,
“We are obviously very disappointed with the unanticipated outcome of the study,” Christopher J. Schaber, PhD, president and chief executive officer of Soligenix, stated in a news release. “Despite the fact that HyBryte demonstrated statistically significant reductions in CTCL lesions after 6 weeks treatment in the first FLASH study, a similar signal was not observed with 18 weeks of treatment in [FLASH2]. Over the coming weeks, we will analyze the data to better determine why the study did not meet expectations. If there is any clarity gained from further analysis of the dataset, especially with respect to specific subsets of patients that may benefit from HyBryte therapy, then we intend to communicate our findings and explore follow-up discussions with the EMA and the US FDA.”
In the initial FLASH trial, patients with stage IA to IIA CTCL/mycosis fungoides were randomly assigned 2:1 to receive HyBryte or placebo, with treatment administered to 3 index lesions twice per week for 6 weeks during cycle 1.3 In cycle 2, all patients received HyBryte directed at index lesions for 6 weeks. In the optional third cycle, HyBryte was targeted at index and additional lesions for 6 weeks.
Interim Analysis of FLASH2: HyBryte in Early-Stage CTCL
Findings from FLASH published in JAMA Dermatology showed that after cycle 1, patients treated with HyBryte (n = 116) experienced an index lesion response rate (ILRR) of 16% compared with 4% for patients given placebo (n = 50; P = .04). After cycle 2, patients given HyBryte in both cycles experienced an ILRR of 40%, and the ILRR was 49% after cycle 3 among patients who received the experimental therapy for all 3 cycles.
FLASH2 was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled patients at least 18 years of age with stage IA, IB, or IIA CTCL who had a minimum of 3 evaluable, discrete lesions.2
Patients were randomly assigned to received 18 weeks of HyBryte or placebo. HyBryte or placebo was applied twice weekly, with treated lesions covered in opaque material, followed by the administration of visible light 21 hours later (± 3 hours). Although all lesions were eligible for treatment, 3 to 5 index lesions were prospectively identified and evaluated using modified Composite Assessment of Index Lesion Severity (mCAILS) criteria.
Response rate at week 18, defined as an improvement of at least 50% in cumulative mCAILS score, served as the trial’s primary end point. Secondary end points included patch lesion response rates and plaque lesion response rates.
