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Vispa-Cel, an Allogeneic Anti-CD19 CAR-T cell Therapy with a PD-1 Knockout, In Patients with relapsed/refractory B cell Non-Hodgkin Lymphoma (r/r B-NHL): Updated Results from the Antler Phase 1 Clinical Trial
Abstract   Peer reviewed

Vispa-Cel, an Allogeneic Anti-CD19 CAR-T cell Therapy with a PD-1 Knockout, In Patients with relapsed/refractory B cell Non-Hodgkin Lymphoma (r/r B-NHL): Updated Results from the Antler Phase 1 Clinical Trial

Mehdi Hamadani, Houston Holmes, James Essell, Ayad Hamdan, Boyu Hu, Elizabeth Brem, Rushang D Patel, Sunita Nasta, Costas K Yannakou, Mohamad Cherry, …
Transplantation and cellular therapy, Vol.32(3 Supplement), pp.S1-S1
03/2026
DOI: 10.1016/j.jtct.2026.02.013

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Abstract

Vispacabtagene regedleucel (vispa-cel, formerly CB-010) is an allogeneic anti-CD19 CAR-T cell therapy manufactured from healthy donor T cells. The Cas9 chRDNA genome-editing technology is used for three genome edits: (1) KO of TRAC to reduce risk of GvHD, (2) insertion of a CD19-specific CAR (FMC63 scFv, 4-1BB), and (3) KO of PD-1 to prevent premature CAR-T cell exhaustion and potentially enhance antitumor activity. ANTLER is a Phase 1 trial (NCT04637763) with 3+3 dose escalation and expansion to evaluate the safety and efficacy of vispa-cel in patients (pts) with r/r B-NHL and determine the RP2D. All pts received lymphodepletion of sequential cyclophosphamide (60 mg/kg/day x 2 days) then fludarabine (25 mg/m2/day x 5 days) followed by a single infusion of vispa-cel. Three vispa-cel doses (40 million [M], 80M, and 120M cells) were evaluated in dose escalation and dose expansion. 80M cells was selected as the RP2D. Subsequently, a 22-pt 2L LBCL confirmatory cohort prospectively evaluated donor-recipient matching ≥4 HLA alleles. A retrospective analysis was performed and identified LBCL pts treated with vispa-cel manufactured from a young donor (<30 yrs) and ≥2 matched HLA alleles, reported as the optimized cohort (N=35). As of Sep 2025, 84 pts received vispa-cel including 67 2L LBCL pts. The median age was 66 years (20-86). Of the 2L LBCL pts, 40 pts (60%) had an aaIPI score of ≥2. Vispa-cel was generally well tolerated; no GvHD was observed. The most common grade (Gr) ≥3 TEAEs were thrombocytopenia (60%), anemia (43%), and neutropenia (36%). By day 60, the neutropenia and thrombocytopenia recovery to Gr ≤2 was 95% and 86%, respectively. CRS occurred in 55% of pts (1% Gr ≥3). ICANS occurred in 14% of pts (5% Gr ≥3). In the 2L confirmatory cohort, ORR was 82% and CR rate was 64%. Median PFS and DOR were not reached (NR) with a 12-month PFS of 51%. Donor age (<30 yrs) and ≥2 matched HLA alleles were identified as covariates associated with improved PFS. In this optimized cohort, ORR was 86% and CR rate was 63%. The median PFS and DOR were NR with a 12-month PFS of 53%. Data from pts treated with vispa-cel from older donor (≥30 yrs) T cells and/or with <2 HLA alleles matched will also be reported. Peak expansion occurred days 7-10 with persistence of up to 30 days post-infusion. Endogenous T and NK cells recovered rapidly in peripheral blood (∼4 weeks) post-infusion, with B cell recovery in all pts by ∼300 days. Vispa-cel is an allogeneic CAR-T cell therapy that results in deep and durable responses on par with approved autologous CAR-T cell therapies in 2L LBCL pts with a generally well-tolerated safety profile supporting outpatient administration. Improved PFS was observed in pts treated with vispa-cel manufactured from young donors and ≥2 matched HLA alleles. A randomized controlled pivotal trial in 2L LBCL pts who are ineligible for both autologous CAR-T and transplant is being planned.

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