FDA Grants Priority Review to SH-111 for Pediatric T-ALL

The FDA has granted priority review to the sterile injectable therapy SH-111 for the treatment of pediatric patients with T-cell leukemia (T-ALL), announced Shorla Pharma Limited, in a press release.¹

“We’re very proud that SH-111 will have a significant clinical benefit particularly for children with leukemia,” said Sharon Cunningham, chief executive officer and co-founder of Shorla Pharma, in a statement. “It’s a desperately needed product and a life-changing treatment that we are honored to bring to patients in the United States, and later, worldwide.”

SH-111 is intended to help both adult and pediatric patients age 1 year and older whose disease has not responded to or has relapsed following treatment with at least 2 chemotherapy regimens. Ireland-based Shorla Pharma expects that the agent will represents a new standard-of-care treatment in particular for children with T-ALL.

T-ALL is characterized by its aggressive nature and tendency to progress rapidly. The field has an urgent need to address this disease in pediatric patients, as they are more likely to develop T-ALL compared with adults.

It was recommended that new treatment strategies for pediatric T-ALL be developed in 2017 based on preclinical research outlining the heterogeneity and the genomic and epigenomicstability of the disease.² Since then, clinical trial investigators have begun the exploration of chimeric antigen receptor (CAR) T cells for the treatment of adult patients with relapsed or refractory T-ALL. One such investigation is the study of the CAR T-cell agent TruUCAR GC027, for which data were presented during the 2020 AACR Annual Meeting andshowed the clinical activity and tolerability of the agent in this patient population.3

In the study, patients received a single infusion of CAR T cell at either 6 × 10⁶ cells/kg (dose level 1; n = 1) and 1.5 × 10⁷ cells/kg (dose level 3; n = 1, and 1 × 10⁷ cells/kg (dose level 2; n = 3). Investigators assessed the incidence in adverse events in the patients doses, as well as response, and CAR T-cell expansion.

Minimal residual disease (MRD)–negative complete responses (CRs) were observed with TruUCAR GC027 in 4 patients following their 28th dose of CAR T cells. Three out of the 4 patients remained 3 of them remained MRD-negative at follow-up and re-evaluations. At the time the data were reported, a fifth patient had also achieved an MRD-negative CR.

In terms of tolerability, grade 3 cytokine release syndrome (CRS) was observed in 4 patients. A grade 4 CRS event was observed in 1 patient who also showed elevated interleukin (IL)-6, IFNγ, and TNFα levels. Investigator noted that the CRS cases were manageable though with supportive care following treatment. No patients in the study experienced neurotoxicity or developed graft-versus-host disease. Finally, 1 patient experienced prolonged cytopenia due to fungal infection and was treated with anti-fungal therapy.

Patient were eligible for inclusion in the study if they were between the ages of 18 and 70 years old with relapsed/refractory T-ALL that is positive for CD7 expression via flow cytometry or immunohistochemistry. Patients were required to have a life expectancy of more than 3 months, an ECOG performance status of 0 to 2, and be able to undergo allogeneic hematopoietic stem cell transplant. The study excluded patients with active infections, major organ dysfunction, or extramedullary or central nervous system involvement.

_References:

_{1. Shorla Pharma announces FDA filing acceptance and Priority Review for T-cell leukemia treatment. News release. Shorla Pharma Limited. April 23, 2021. Accessed April 23, 2021. https://bwnews.pr/3ngUKYU}

_{2. Doebentz C, Richter-Penchanska P, Frismantas V, et al. PDX models recapitulate genetics and epigenetics of pediatric t-cell leukemia. Blood. 2017;130(suppl 1):2723. doi:10.1182/blood.V130.Suppl_1.2723.2723}

_{3. Wang X, Li S, Gao L, et al. Clinical safety and efficacy study of TruUCAR GC027: the first-in-human, universal CAR-T therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). Presented at: 2020 American Association for Cancer Research Annual Meeting I; April 27-28, 2020; Virtual. Abstract CT052.}