FDA Grants Fast Track and Rare Pediatric Disease Designation to WU-CART-007 in R/R T-Cell ALL/LBL

The FDA has granted fast track designation and rare pediatric disease designation to WU-CART-007 for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL), according to a press release from Wugen.

A first-in-human phase 1/2 study (NCT04984356) is ongoing analyzing the safety and efficacy of WU-CART-007 in relapsed/refractory T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma. WU-CART-007 is an allogeneic, off-the-shelf, fractricide-resistant CD7-targeted CAR T-cell therapy that harnesses CAR T cells to treat CD7-positive hematological malignancies. CRISPR/Cas9 gene editing technology was utilized to eliminate CD7 and T-cell receptor alpha constant to mitigate CAR T-cell fratricide and reduce the possibility of graft-versus-host disease.

“We are very pleased to have received both fast track and rare pediatric disease designations, which re-affirm the great unmet need for new treatment options for people with relapsed/refractory T-ALL/LBL,” Dan Kemp, PhD, president and chief executive officer of Wugen, said in a press release. “Earlier this year, we dosed the first patient in our ongoing phase 1/2 trial of WU-CART-007 for relapsed/refractory T-ALL/LBL and are currently in the dose escalation phase of the study. We look forward to working closely with the FDA as we continue to advance WU-CART-007 through clinical development.”

The trial has an estimated enrollment of 44 patients. The phase 1 portion of the study is comprised of a dose escalation and phase 2 will be the expansion phase. Patients will receive WU-CART-007 through an intravenous infusion on day 1 after lymphodepleting therapy consisting of 500 mg/m² of cyclophosphamide per day for days ­­­–5 to –3 and 30 mg/m²of fludarabine per day on days –5 to –3.

The primary end points of the trial are the incidence of adverse effects, maximum tolerated dose, overall response rate, duration of response, and progression-free survival. The secondary end points are overall survival and hematopoietic stem cell transplant rate.

Patients were eligible for the study if they had relapsed/refractory T-cell ALL or T-cell LBL which was defined by the World Health Organization as having bone marrow with 5% or more lymphoblasts by morphologic assessment or having evidence of extramedullary disease. Patients must also have an adequate renal, hepatic, respiratory, and cardiovascular function; a life expectancy of more than 12 weeks; be between 12 to 17 years old for the adolescent portion of the trial; and have an ECOG or Karnofsky performance status of 0 to 1 for adults older than 16 and a Lansky performance score of 60 and above for those younger than 16. Additionally, patients must be able to comprehend the nature of the study and comply with the protocol requirements or give written or informed consent and continue with long-term follow-up.

Exclusion criteria included having previous treatment with an anti-CD7 therapy, not having recovered from previous therapy, and a wash-out period of a minimum of 5 half-lives from the last date to any investigational therapy prior to the screening period. Additional criteria were having active or latent hepatitis B or C or uncontrolled infection, or being human immunodeficiency virus–positive; having a serious active infection when beginning treatment or another underlying medical condition that could hinder receipt of protocol treatment; grade 2 to 4 graft-versus-host disease that required immunosuppression steroids; having a psychological, familial, sociological, or geographical conditions that do not permit compliance with the treatment protocol.

Reference

Wugen received US FDA fast track and rare pediatric disease designation for WU-CART-007 for the treatment of R/R T-ALL/LBL. News Release. Wugen. July 19, 2022. Accessed July 20, 2022. https://bit.ly/3yP4CiW