WU-CART-007 Receives FDA RMAT and EMA PRIME Designations for R/R T-ALL and T-LBL

The allogeneic CAR-T cell therapy WU-CART-007 has received regenerative medicine advanced therapy (RMAT) designation by the FDA and priority medicines (PRIME) designation by the European Medicines Agency (EMA) for the treatment of patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL).¹

In an announcement from to Wugen, the agent’s developer, the company said it anticipates that these designations will support and expedite regulatory review of the agent on 2 continents.¹

These regulatory designations were supported by data from a global phase 1/2 trial (NCT04984356). Data presented at the 2023 ASH Annual Meeting demonstrated that patients treated with WU-CART-007 at dose level 2 or higher (n = 18) experienced an objective response rate of 78%; this included a composite complete response (CRc) rate of 67%, comprising CRs, CRs with partial hematologic recovery (CRh), CR with incomplete count recovery (CRi), and morphologic leukemia–free state (MFLS). Additionally, 10 of 11 evaluable patients achieved minimal residual disease negativity following treatment (91%).²

Notably, enhanced lymphodepletion in the phase 2 portion led to a 100% ORR at the recommended phase 2 dose (RP2D) of 900 x 10⁶ CAR T cells. The agent also demonstrated an overall acceptable safety profile.

Updated phase 2 results from this study will be presented during the 2024 EHA Congress.¹

“The FDA and EMA granted these designations for WU-CART-007 based on the rigor of our data and the potential of WU-CART-007 in addressing serious unmet needs of patients suffering from resistant blood cancers following treatment with current therapies,” Jan Davidson-Moncada, MD, PhD, chief medical officer of Wugen, stated in a press release.

WU-CART-007 is an off-the-shelf, fratricide-resistant, CD7-targeted CAR T-cell therapy designed to address challenges associated with harnessing CAR T-cells for the management of CD7-positive hematological malignancies. The agent was previously granted both fast track and rare pediatric disease designations by the FDA for relapsed/refractory T-ALL and T-LBL in July 2022.³

This ongoing, global, open-label study of WU-CART-007 is enrolling patients with relapsed/refractory T-ALL or T-LBL, as defined by the World Health Organization classification with bone marrow blasts of at least with 5% or evidence of extramedullary disease at screening.⁴ Patients must have undergone allogeneic hematopoietic stem cell transplant (HSCT) more than 90 days prior to enrollment from a match-related or unrelated donor; cord blood donor; a haplo-identical donor; or autologous stem cells. Additional inclusion criteria consisted of an ECOG or Karnofsky performance status of 0 or 1 at screening; adequate renal, hepatic, respiratory, and cardiovascular function; and a life expectancy of more than 12 weeks.

The lower age limit of the trial was 12 years, and patients between 12 and 17 years of age were permitted to enroll at dose level 3 of the dose-escalation portion of the trial following a review of safety, efficacy, and cellular pharmacokinetics, and consultation with regulatory agencies.

Upon enrollment in the dose-escalation portion of the trial, patients underwent lymphodepletion with a daily dose of 500 mg/m² of cyclophosphamide and 30 mg/m² of fludarabine 30 mg/m² on days –5 to –3. On day 1, patients were administered an intravenous infusion of WU-CART-007 at 1 of 4 dose levels: 100 x 10⁶, 300 x 10⁶, 600 x 10⁶, or 900 x 10⁶ CAR T cells. In the phase 2 dose-expansion portion, patients will receive an enhanced lymphodepletion regimen comprising a daily dose of 1000 mg/m² of cyclophosphamide on days –5, –4, and –3, along with 30 mg/m² of fludarabine on days –6, –5, –4, and –3.²

The primary end points of the trial included the incidence of adverse effects, establishing the maximum tolerated dose, and CRc rate. Key secondary end points included ORR, duration of response, overall survival, and HSCT rate.⁴

Wugen plans to initiate a follow-up study of WU-CART-007 in pediatric patients and those with MRD in the final quarter of 2024.¹

References

1. Wugen announces RMAT and PRIME designations for WU-CART-007 to accelerate regulatory reviews and plans to present positive phase 2 study findings at European Hematology Association (EHA) 2024 in June. News Release. Wugen. May 20, 2024. Accessed May 20, 2024. https://wugen.com/wugen-announces-rmat-and-prime-designations-for-wu-cart-007-to-accelerate-regulatory-reviews-and-plans-to-present-positive-phase-2-study-findings-at-european-hematology-association-eha-2024-in-june/
2. Ghobadi A, Aldoss I, Maude SL, et al. Phase 1/2 dose-escalation/dose-expansion study of anti-CD7 allogeneic CAR-T Cells (WU-CART-007) in relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia/ lymphoblastic lymphoma (T-ALL/LBL). Blood. 2023;142(suppl 1):770.https://doi.org/10.1182/blood-2023-178723.
3. Wugen receives US FDA fast track and rare pediatric disease designations for WU-CART-007 for the treatment of R/R T-ALL/LBL. News release. Wugen. July 19, 2022. Accessed May 20, 2024. https://wugen.com/wugen-receives-u-s-fda-fast-track-and-rare-pediatric-disease-designations-for-wu-cart-007-for-the-treatment-of-r-r-t-all-lbl/
4. A phase 1/​2 study of the safety and efficacy of anti-CD7 allogeneic CAR-T cells (WU-CART-007) in patients with relapsed or refractory T-ALL/​LBL. ClinicalTrials.gov. Updated Nov 24, 2023. Accessed May 20, 2024. https://clinicaltrials.gov/study/NCT04984356