Caribou Biosciences, Inc. reported long-term follow-up data from the dose escalation portion of the ongoing ANTLER Phase 1 trial. The data set includes all 16 patients treated in dose escalation with CB-010, an allogeneic anti-CD19 CAR-T cell therapy being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). In ANTLER dose escalation, three dose levels of CB-010 were evaluated (40x106, 80x106, and 120x106 CAR-T cells) in patients with multiple subtypes of aggressive r/r B-NHL.

As of the data cutoff date, results demonstrated: CB-010 was generally well tolerated with adverse events consistent with autologous or allogeneic anti-CD19 CAR-T cell therapies; as previously reported, no dose-limiting toxicities (DLTs) were observed at dose levels 2 or 3 following a single DLT at dose level 1. 94% overall response rate (ORR; 15 of 16 patients) was observed following a single dose of CB-010. 69% of patients (11 of 16) achieved a complete response (CR). 44% of patients (7 of 16) had a CR at =6 months; 24 months is the longest CR maintained to date.

For the subset of patients with large B cell lymphoma (LBCL) (N=10): A 90% ORR (9 of 10) was observed. 70% (7 of 10) achieved a CR. 50% (5 of 10) had a CR at =6 months; 18 months is the longest CR maintained to date.

Each of the 16 patients had aggressive r/r B-NHL and had received two or more prior lines of chemoimmunotherapy or were primary refractory patients. Based on these positive data, Caribou is enrolling second-line patients with LBCL in the ongoing dose expansion portion of the ANTLER clinical trial. In expansion, the mid dose and the high dose from escalation (80x106 and 120x106 CAR-T cells) are being evaluated in approximately 30 second-line patients (approximately 15 patients per dose level) to determine the recommended Phase 2 dose (RP2D).

Once the RP2D is determined, Caribou may enroll additional patients in ANTLER. Caribou plans to report initial dose expansion data from the ongoing ANTLER trial in first half 2024. To Caribou’s knowledge, CB-010 is the first allogeneic anti-CD19 CAR-T cell therapy in the clinic to be evaluated in second-line LBCL patients and CB-010 is also the first allogeneic anti-CD19 CAR-T cell therapy in the clinic with a PD-1 knockout, a genome-editing strategy designed to enhance antitumor activity by limiting premature CAR-T cell exhaustion.

To Caribou’s knowledge, CB-010 is the first allogeneic anti-CD19 CAR-T cell therapy in the clinic to be evaluated in second-line LBCL patients and CB-010 is also the first allogeneic anti-CD19 CAR-T cell therapy in the clinic with a PD-1 knockout, a genome-editing strategy designed to enhance antitumor activity by limiting premature CAR-T cell exhaustion. CB-010 was generally well tolerated with adverse events consistent with autologous or allogeneic anti-CD19 CAR-T cell therapies. No grade 3+ cytokine release syndrome (CRS) and no graft-vs-host disease (GvHD) cases were observed.

The most common adverse events included thrombocytopenia (69% Grade 3+), neutropenia (56% Grade 3+), and anemia (50% Grade 3+).