CB-010 Exhibits Impressive Early Efficacy in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

The CAR T-cell therapy CB-010 displayed promising preliminary efficacy and safety results in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) according to findings from the phase 1 ANTLER trial (NCT04637763) presented during the 2022 Pan Pacific Lymphoma Meeting.

All 6 efficacy-evaluable patients who had been treated with a single infusion of CB-010 at the May 13, 2022, data cutoff experienced a complete response (CR). The longest measured CR lasted 9 months and 40% of patients were still in CR at 6 months. Three patients experienced progressive disease and the remaining 3 are continuing on study.

CB-010 is an allogeneic CD19-directed CAR T-cell agent that contains a PD-1 knock out. The absence of PD-1 receptors on their surface makes CB-010 cells insensitive to PD-L1 interaction. In preclinical studies, CB-010 was shown to maintain persistent tumor eradication for a longer duration compared with conventional allogeneic CAR T cells.

ANTLER included patients with relapsed/refractory B-cell NHL who had received at least 2 prior lines of chemoimmunotherapy. Patients who were previously treated with a CD19-targeted therapy were excluded.

Part A of the trial is a 3 + 3 dose escalation. The objectives of part A are safety, determining the maximum-tolerated dose, and determining the recommended phase 2 dose. Part B of ANTLER is the dose-expansion portion, and the objective is tumor response.

CB-010 is being administered at 2 dose levels: 40 × 10⁶ CAR-positive cells and 80 × 10⁶ CAR-positive cells. All 6 patients included in the efficacy analysis that was presented at the 2022 Pan Pacific Lymphoma Meeting received the lower dose. Enrollment for the higher dose is ongoing.

The median age of patients in the efficacy population was 65 years (range, 62-68) and most patients were males (83%). Most patients had an ECOG performance status of 0 (83%) and all patients had CD19-positive disease. The median number of prior systemic therapies was 3 (range, 2-8) and the median time since first diagnosis was 6 years (range, 0.7-16).

The NHL subtypes included in the trial consisted of diffuse large B-cell lymphoma (n = 2), follicular lymphoma (n = 2), mantle cell lymphoma (n = 1), and primary mediastinal large B-cell lymphoma (n = 1).

In terms of safety, study authors noted that CB-010 was generally well tolerated. All patients experienced a treatment-emergent adverse effect (TEAE) of any grade, 83% of patients experienced a TEAE of at least grade 3, and 67% of patients experienced a TEAE related to CB-010.

Common TEAEs of any grade included neutropenia (83%), thrombocytopenia (67%), anemia (67%), decreased white blood cell count (50%), and decreased lymphocyte count (50%). Grade 3 or greater TEAEs consisted of neutropenia (83%), thrombocytopenia (67%), decreased white blood cell count (50%), and anemia (33%). Three patients each experienced treatment-related grade 3 or greater thrombocytopenia and decreased white blood cell count.

Investigators identified cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections as adverse effects of special interest.

Both instances of CRS were grade 1. The median time to onset of CRS was 4 days (range, 1-7) and the median duration of a CRS event was 8 days (range, 7-8).

There was 1 grade 1 ICANS event. The time to onset of the event was 8 days and it lasted approximately 39 hours.

One patient experienced a grade 2 infection, and 1 patient experienced a grade 3 infection. The median time to onset was 8.5 days (range, 2-140) and the median duration of an event was 5 (range, 1-56).

Reference

Nastoupil LJ, O’Brien S, Dsouza L, et al. First-in-human trial of CB-010, a CRISPR-edited allogeneic anti-CD19 CAR T-cell therapy with a PD-1 knock out, in patients with relapsed or refractory B cell non-Hodgkin lymphoma (ANTLER study). Presented at: 2022 Pan Pacific Lymphoma Conference. July 18-22, 2022; Koloa, Hawaii.