New CAR T-Cell Therapy Earns FDA Breakthrough Status in T-Cell Malignancies

The FDA has conferred breakthrough therapy designation to soficabtagene geleucel (sofi-cel; WU-CART-007) as a treatment for patients with relapsed/refractory T-cell acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic lymphoma (LBL), according to a press release from the developer, Wugen, Inc.¹

Developers created sofi-cel as an allogenic, off-the-shelf CAR T-cell therapy that targets CD7. With the use of CRISPR/Cas9 gene editing technology to delete CD7 and TRAC genes, the novel therapy may prevent CAR T-cell fratricide and mitigate the risk graft-versus-host-disease (GVHD). Additionally, developers can manufacture the product via healthy donor-derived T cells, thereby reducing the risk of malignant cell contamination associated with other autologous CAR T-cell agents.

“The FDA’s breakthrough therapy designation underscores the promising clinical data we have generated and the potential for sofi-cel to make a meaningful difference for patients with relapsed or refractory T-ALL/LBL,” Cherry Thomas, MD, chief medical officer at Wugen, stated in the press release.¹ “This recognition enables close collaboration with the FDA to accelerate development and, ultimately, help bring this innovative therapy to patients as quickly as possible.”

Supporting data for the breakthrough therapy designation came from a phase 1/2 trial (NCT04984356) assessing sofi-cel among those with relapsed/refractory T-cell malignancies. Findings published in Blood showed an overall response rate (ORR) of 90.9% among 11 evaluable patients who received enhanced lymphodepleting chemotherapy plus the recommended phase 2 dose (RP2D) of sofi-cel, which included a complete remission (CR) rate of 72.7%.

The most common adverse effect (AE) of any grade was cytokine release syndrome (CRS; 88.5%); grade 3/4 events were reported in 19.2% of patients. Investigators noted 2 instances of grade 1 immune effector cell–associated neurotoxicity syndrome (ICANS; 7.7%), 1 instance of grade 2 acute GVHD (3.8%), and 1 instance of grade 2 ICANS-related hemophagocytic lymphohistiocytosis–like syndrome.

Investigators of the phase 1/2 study used a 3+3 dose-escalation design followed by cohort expansion to assess treatment with sofi-cel among those with relapsed/refractory T-cell malignancies. Of 28 patients enrolled on the trial, 13 received the agent at the RP2D of 900 x 10⁶ cells plus enhanced lymphodepletion. The trial’s primary objectives were determining the safety and the composite CR rate of sofi-cel.

Patients 12 years and older with relapsed or refractory T-cell ALL or LBL based on World Health Organization guidelines and adequate renal, hepatic, respiratory, and cardiovascular function were eligible for enrollment on the study.³ Having a life expectancy of more than 12 weeks and an ECOG performance status of 0 or 1 or a Lansky performance status of 60 or higher among patients 16 years and older were additional requirements for study entry.

Investigators are also assessing the safety and efficacy of sofi-cel among patients with relapsed/refractory T-cell ALL and LBL as part of the pivotal phase 2 T-RRex study (NCT06514794). Developers also plan to launch an exploratory cohort of sofi-cel among patients with minimal residual disease (MRD).

In the T-RRex study, patients will receive sofi-cel as a single intravenous infusion.⁴ Trial end points include the composite CR rate in the relapsed/refractory cohort as well as response rate in the MRD-positive cohort. Patients 1 year and older with evidence of T-cell ALL or LBL based on WHO classification and relapsed/refractory or MRD-positive status are eligible for enrollment on the trial.

“Our goal is to bring this investigational off-the-shelf allogeneic CAR-T treatment to patients as soon as possible. Receiving breakthrough therapy designation from the FDA is a significant milestone for our company and a testament to the potential of our therapy to address a critical unmet medical need,” Kumar Srinivasan, PhD, MBA, president and chief executive officer at Wugen, concluded in the press release.¹

References

1. U.S. FDA grants to Wugen’s WU-CART-007 breakthrough therapy designation for treatment of relapsed or refractory T cell acute lymphoblastic leukemia / T cell lymphoblastic lymphoma. News release. Wugen, Inc. January 21, 2026. Accessed January 22, 2026. https://tinyurl.com/mu5rzuak
2. Ghobadi A, Aldoss I, Maude SL, et al. Phase 1/2 trial of anti-CD7 allogeneic WU-CART-007 for patients with relapsed/refractory T-cell malignancies. Blood. 2025;146(10):1163-1173. doi:10.1182/blood.2025028387
3. A phase 1 study of of anti-CD7 allogeneic CAR-T cell therapy (WU-CART-007) in patients with relapsed or refractory T-ALL/​LBL. ClinicalTrials.gov. Updated September 30, 2025. Accessed January 22, 2026. https://tinyurl.com/z5fd4beu
4. A phase 2 study of WU-CART-007, an anti-CD7 allogeneic CAR-T cell therapy in T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-RRex). ClinicalTrials.gov. Updated January 5, 2026. Accessed January 22, 2026. https://tinyurl.com/4jm5adyc