Anbalcabtagene autoleucel (anbal-cel; CRC01), a novel autologous anti-CD19 CAR T-cell therapy, produced durable responses and demonstrated favorable tolerability in patients with relapsed/refractory large B-cell lymphoma (LBCL), according to interim data from a phase 2 trial presented at the 17th Annual International Conference on Malignant Lymphoma.
The study showed that evaluable patients treated with anbal-cel (n = 38) achieved an objective response rate (ORR) of 84% per independent review committee (IRC) assessment. This included a complete response (CR) rate of 71% and a partial response (PR) rate of 13%. Additionally, 3% of patients had stable disease, 5% experienced progressive disease, and 8% were not evaluable.
"During the primary evaluation, we saw excellent and encouraging efficacy with anbal-cel," said lead study author Won-Seog Kim, MD, PhD, a professor in the Division of Hematology-Oncology at Samsung Medical Center in Seoul, South Korea. "[Responses] seem quite durable, particularly after 3 months."
Novel CAR T-Cell Platform Technology
Anbal-cel is based on the first-in-class CAR T platform, OVIS, which is being developed by Curocell. OVIS downregulates PD-1 and TIGIT expression on CAR T cells with the goal of delivering improved cytotoxicity to tumor cells in the tumor microenvironment.
Prior data from the phase 1 dose-escalation portion of the trial showed that 11 patients treated across 3 different dose levels of anbal-cel experienced an ORR of 82%, with all responders achieving a CR. The CR rates at doses of 2 x 10⁵ cells/kg (n = 4), 7 x 10⁵ cells/kg (n = 3), and 2 x 10⁶ cells/kg (n = 4) were 75%, 67%, and 100%, respectively.
Study Design and Patient Population
The phase 2 trial enrolled patients with diffuse LBCL not otherwise specified (DLBCL-NOS), high-grade B-cell lymphoma (HGBL), primary mediastinal LBCL, or transformed follicular lymphoma who received at least 2 prior lines of therapy; however, prior CD19 targeted therapy was not allowed. Other inclusion criteria included measurable disease and an ECOG performance status of 0 or 1.
Following leukapheresis, bridging chemotherapy was optional. All patients received lymphodepleting chemotherapy with 30 mg/m² of fludarabine and 500 mg/m² of cyclophosphamide on days −5, −4, and −3. Patients in phase 2 received a single infusion of anbal-cel at 2 x 10⁶ cells/kg.
In phase 2, 47 patients underwent leukapheresis as of the April 11, 2023, data cutoff. Six patients did not receive the CAR T-cell therapy due to a failure in manufacturing (n = 4) and not meeting the dosing requirements for anbal-cel (n = 2). Twenty-five patients underwent bridging therapy consisting of bendamustine plus rituximab (n = 9); gemcitabine, dexamethasone, and cisplatin (n = 5); cyclophosphamide, vincristine, and prednisone (n = 4); dexamethasone, high-dose cytarabine, and cisplatin (n = 2); vincristine (n = 2); and other (n = 3).
Patient Characteristics and Disease Burden
Among the safety-evaluable population, the median age was 62.8 years (range, 53-72), and 54% of patients were at least 65 years of age. Most patients were male (63%), had DLBCL-NOS (93%), had non–germinal center B-cell cell of origin (76%), and had double expressor type (66%). Twenty-four percent of patients had an ECOG performance status of 1.
Seventy-three percent of patients received 1 or 2 prior lines of therapy, 17% had 3 prior lines of therapy, and 10% were given 4 or more prior lines of therapy. Fifty-six percent of patients were refractory to their last line of therapy, and 56% of patients were refractory to their first line of therapy. Additionally, 71% of patients received prior stem cell transplant.
The median sum of the product of perpendicular diameters (SPD) was 2951 mm² (range, 1099-4361), and 20% of patients had a SPD of at least 5000 mm². The median total metabolic tumor volume was 78 (range, 27-218).
Sustained Response Rates
Additional data showed that at a median follow-up of 6.3 months, 68% of patients (n = 26/38) were in CR at 1 month, 61% (n = 19/31) were in CR at 3 months, and 60% (n = 12/20) were in CR at 6 months, per IRC assessment. The investigator-assessed CR rates at 1, 3, and 6 months were 66%, 68%, and 65%, respectively.
Safety Profile
Regarding safety, all patients experienced any-grade and grade 3 or higher treatment-emergent adverse effects (TEAEs). Thirty-four percent of patients experienced any serious AE, 5% had a TEAE with a fatal outcome, and 5% dropped out of the study due to a TEAE. The rates of drug-related TEAEs, grade 3 or higher TEAEs, and serious AEs were 90%, 88%, and 24%, respectively.
Any-grade cytokine release syndrome (CRS) was reported in 63.4% of patients, and 14.6% of patients had grade 3 CRS. The median time to CRS onset was 2.0 days (range, 2-3), and the median duration of CRS was 6.5 days (range, 4-10). Eighty-one percent of patients with CRS received tocilizumab, 35% were given steroids, and 23% received a vasopressor.
Any-grade neurologic events occurred in 19.5% of patients, including grade 1 (4.9%), grade 2 (7.3%), and grade 3 (7.3%). The median time to onset of neurologic events was 6.5 days (range, 3-8), and the median duration was 10.5 days (range, 2-91). Rescue medication for neurologic events included tocilizumab (13%), steroids (88%), and antiepileptics (38%).
Other AEs of special interest included prolonged neutropenia (31.7%), prolonged thrombocytopenia (34.1%), prolonged anemia (14.6%), and serious infection (9.8%).
Cellular Kinetics and Response Correlation
Cellular kinetic data showed that patients who achieved a CR had a greater mean Cmax (58,500 vs 31,300) and a greater mean AUC0-28D (653,600 vs 343,800) vs non responders, suggesting a correlation between CAR T-cell expansion and clinical response.
