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

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

“We are very proud that SH-111 will have significant clinical benefit, especially for children with leukemia,” Sharon Cunningham, CEO and co-founder of Shorla Pharma, said in a statement. “It is a much-needed product and a life-changing treatment that we are honored to offer to patients in the United States and later worldwide.”

SH-111 is intended to help both adult and pediatric patients 1 year of age and older whose disease has not responded to or has relapsed after treatment with at least 2 chemotherapy regimens. Ireland-based Shorla Pharma expects it to represent a new standard of treatment, especially for children with T-ALL.

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

It was recommended that new treatment strategies for pediatric T-ALL be developed in 2017 based on preclinical research outlining the heterogeneity, genomic and epigenomic stability of the disease.2 Since then, clinical trial investigators have begun to investigate the chimeric antigen receptor (CAR). T cells for the treatment of adult patients with relapsed or refractory T-ALL. One such study is the study of the CAR T cell agent TruUCAR GC027, for which data was presented at the 2020 AACR annual meeting and demonstrated the drug’s clinical activity and tolerability in this patient population.3

In the study, patients received a single infusion of CAR T cell at 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). kg (dose level 3; n = 1 and 1 × 107 cells / kg) .cells / kg (dose level 2; n = 3) Investigators assessed the incidence of adverse reactions at the patient’s 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 after their 28th dose of CAR T cells. Three of the 4 patients remained and 3 of them remained MRD negative at follow-up and re-evaluation. At the time the data was 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 exhibited elevated levels of interleukin (IL) -6, IFNγ, and TNFα. The investigator noted that the CRS cases were manageable, although with supportive care after treatment. None of the patients in the study experienced neurotoxicity or developed graft versus host disease. Finally, 1 patient experienced long-term cytopenia due to a fungal infection and was treated with antifungal therapy.

Patients were eligible for enrollment if they were aged between 18 and 70 years with relapsed / refractory T-ALL positive for CD7 expression by 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 an allogeneic haematopoietic stem cell transplant. The study excluded patients with active infections, severe organ dysfunction, or extramedullary or central nervous system involvement.

References:

1. Shorla Pharma Announces FDA Approval and Priority Review for the Treatment of T-Cell Leukemia. 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 the 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 universal CAR-T therapy in humans for relapsed / refractory T-cell acute lymphoblastic leukemia (r / r T-ALL) in adults. Presented at: 2020 American Association for Cancer Research Annual Meeting I; April 27-28, 2020; Virtual. Summary CT052.

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