B-cell CAR-T cell therapies have received a lot of attention since there has been significant progress made in that area; the T-cell segment, however, remains untapped. ALL is very common in adolescent and young adult patient populations, which lacks effective therapies. T-ALL accounts for only 10% to 15% of pediatric and up to 25% of adult ALL cases (~ 1,000 T-ALL incident cases as per DelveInsight). Historically, chemotherapy has shown good response rates but roughly 20% children and 40% adults relapse, with 80% of these relapses occurring within 2 years of diagnosis. Relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma (R/R T-ALL/LBL) are difficult to treat, with limited available options. Data suggests that salvage has remained poor in  T-ALL, with less than 25% event-free and overall survival rates for relapsed disease.  In R/R setting WU-CART-007 can be effective. 

Although autologous CAR-T cells have shown success in B-cell malignancies, their development for T-cell malignancies is hindered by issues such as fratricide and the risk of malignant cell contamination in the drug product. WU-CART-007, a CD7-targeted CAR-T cell therapy, employs CRISPR/Cas9 to delete CD7 and the T-cell receptor alpha constant, preventing fratricide and allowing the use of healthy donor allogeneic T-cells.

Wugen previously reported data from the Phase I/II trial at the 2023 American Society of Hematology (ASH) Annual Meeting. Among 18 of 22 evaluable patients treated at the trial’s second dose level or a greater dose, the Composite Complete Remission Rate was 67%. Furthermore, patients treated at the recommended Phase 2 dose level achieved a CRc of 73%. The safety profile for WU-CART-007 was characterized as manageable.

The presentation at EHA 2024 congress showcased results from the WU-CART-007 1001 study (NCT04984356). The administration of the recommended dose (RP2D) of WU-CART-007 was done in 13 heavily pre-treated patients with a median age of 30 years and a high disease burden at the study's onset. Notably, 38% of these patients had relapsed or progressed following an allogeneic stem cell transplant. In Phase II the median prior lines of therapy were 3 (2-6) and 15% of the patients had induction failure.

Also, Read @ CAR T-Cell Therapy for Acute Lymphoblastic Leukemia Market Size

Key outcomes from the WU-CART-007 treatment, surpassed the current standard of care (nelarabrine) for R/R T-ALL/LBL. At RP2D, the CAR-T showed:

• a composite complete remission rate (CRc) of 73% (8/11), the primary endpoint

• an overall response rate (ORR) of 91% (10/11), with 2 partial responses (PR) in patients with extramedullary disease, R/R T-LBL

• median duration (mDOR) of 6.2 months (95% CI: 1.8, NE)

• at a median follow-up of 8.5 months (95% CI: 2.7, NE), 46% (5/11) of patients remained in continuous remission from 4.3 to 8.6 months

• seven patients, including 5 at RP2D, successfully underwent transplantation

Pharmacokinetic analysis exhibited rapid expansion and persistence of an allogeneic cell  therapy:

• At RP2D, WU-CART-007 expansion peaked at Day 10 (223,799 copies/𝝁g of DNA) and can be detected out to Day 90.

• No patient developed drug product-specific anti-HLA antibodies.

• No anti-drug antibody detected on any patients to date.

Read More @ Acute Lymphoblastic Leukemia Market Size

As far as safety is concerned, WU-CART-007 demonstrated manageable safety. Treatment-related adverse events of Grade 3 and higher were observed in 61.5% (n= 16/26) patients. Cytokine Release Syndrome (CRS) was observed in 88.5% (n = 23/26) patients.  Most (69.2%; 18/26) patients had Grade 1-2 CRS events, (11.5%; 3/26) had Grade 3 CRS events, and (7%; 2/26) had Grade 4 CRS events. Grade 4 CRS events were manageable with supportive care and completely resolved within 7 and 13 days, respectively.

Grade 1 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were reported in two patients (7.7%) at dose level (DL3) and RP2D.  Grade 2 HLH was reported in two patients (7.7%) at DL2 and one at the RP2D. Grade 2 GvHD was reported in one patient (3.8%) at RP2D. One Grade 3 prolonged cytopenia manifested as prolonged neutropenia and thrombocytopenia. Grade 5 events were reported in three patients (11.5%); two were deemed not related (1 DL3, 1 RP2D) one (RP2D) of which was temporally related and occurred in the setting of disease progression.

KOL insights

“For a disease that disproportionately affects younger individuals, the need to find better treatments feels especially urgent. It is encouraging to see positive momentum—with favorable tolerability and efficacy data continuing to be reported as the study has expanded to include more patients with such difficult-to-treat blood cancers.” – MD, United States.

Conclusion 

The CAR-T space is currently receiving a lot of attention, and competition follows attention. In the autologous CAR-T segment there is enormous competition. Allogeneic CAR T cells offer several advantages over non-allogeneic CAR T cells, including decreased time to treatment, improved T-cell subset selection, product standardization, and increased potential for redosing. Allogeneic CAR T production may allow broader patient populations to receive therapy by mitigating the need for leukapheresis, reducing antigen burden, and improving tolerability. At the moment, Wugen set itself apart from its rivals. Rather than focusing on B-cell leukemia/lymphoma, the company is targeting the T-cell leukemia/lymphoma subpopulation. Despite the relatively smaller patient pool, this market has a significant unmet demand. 

T-ALL/LBL are challenging hematologic cancers with high rates of mortality in both children and adults. Although B-cell leukemias have responded well to CAR-T treatments, T-cell diseases present unique difficulties. Data from EHA 2024 congress suggests its potential in this difficult to treat segment. Recently, WU-CART-007 has received regenerative medicine advanced therapy (RMAT) and priority medicines (PRIME) designations in R/R T-ALL/LBL. These regulatory designations were supported by data from a global phase I/II trial (NCT04984356). Wugen is planning a follow up study in R/R T-ALL/LBL including pediatric patients <12 years and a minimal residual disease (MRD) cohort is projected to start in Q4 2024.

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