FDA Grants Priority Review to SH-111 for Pediatric T-Cell Leukemia

The FDA has granted a priority review designation to SH-111, a sterile injectable therapy, for the treatment of pediatric patients with T-cell leukemia, according to Shorla Pharma Limited, the developer of the agent.¹

“We’re very proud that SH-111 will have a significant clinical benefit particularly for children with leukemia,” said Sharon Cunningham, CEO and cofounder of Shorla Pharma. “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.”

T-cell leukemia is defined as an aggressive blood and bone marrow cancer with rapid disease progression, noted Shorla, and is most common in children.

SH-111 is designed to target T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in adult and pediatric patients aged 1 year and older whose disease has not responded to or has relapsed following at least 2 chemotherapy regimens.²

“Reaching this milestone is an important step as we continue to make progress across our growing pipeline,” said Orlaith Ryan, Shorla Pharma CTO and cofounder. “Our focus is on developing innovative oncology treatments for women and children, with a focus on rare cancers where existing treatments are limited, in short supply or inadequate.”

Shorla Pharma is based in Ireland.

Additional agents are emerging in the T-ALL pipeline. At the 2020 AACR Annual Meeting, results of the first-in-clinical universal chimeric antigen receptor (CAR) T-cell product TruUCAR GC027 showcased early clinical activity and found to be tolerable in adult patients with relapsed/refractory T-ALL.³ GC027 targets CD7-positive T-cell malignancies using the TruUCAR platform, and is developed by Gracell Biotechnologies.

In this trial, baseline bone marrow burden was analyzed prior to receiving preconditioning regimens. Patients were given a single infusion at one of 3 dose levels: 6 × 10⁶ cells/kg (dose level 1; n = 1) and 1.5 × 10⁷ cells/kg (dose level 3; n = 1), respectively, and 1 × 10⁷ cells/kg (dose level 2; n = 3). Follow-up was done for incidence of adverse events, response to treatment, and CAR T-cell expansion.

To be eligible for enrollment, patients had to be aged between 18 and 70 years and have relapsed/refractory T-ALL that is positive for CD7 expression via flow cytometry or immunohistochemistry; a projected survival greater than 3 months was also required. Additional criteria included an ECOG performance status of 0 to 2 or less and able to undergo allogeneic hematopoietic stem cell transplant (HSCT). Those with active infections, major organ dysfunction, or extramedullary or central nervous system involvement were excluded from enrollment.

Five patients were enrolled. The median age was 24 years (range, 19-38), the median number of prior therapies was 5, and the median tumor burden at baseline was 38.2% of blasts (range, 4-80.2). No patients had received prior allogeneic-HSCT.

Results of the small trial showed that all 5 patients who were evaluated achieved a complete remission (CR) or CR with incomplete hematologic recovery at the first evaluation. Four patients (80%) had a minimal residual disease–negative CR at 1 month.

Moreover, cellular expansion was observed as early as day 5 and continued for 2 weeks. One patient who achieved a CR at day 14 but relapsed at day 29 had the shortest duration of CAR T-cell expansion by quantitative polymerase chain reaction and did not achieve CAR T-cell expansion by flow cytometry.

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/3vebhzU
2. SH-111. Shorla Pharma. April 23, 2021. Accessed April 23, 2021. https://bit.ly/3ngVvBC
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.