Caribou Reports Positive Initial Data for Gene-Edited Allogeneic CAR-T Cell Therapy

Caribou Biosciences reported initial results demonstrating a 100 percent overall response rate (ORR) and 80 percent complete response rate (CR) in five patients with the rare blood cancer relapsed or refractory B cell non-Hodgkin lymphoma who received one dose of CB-010, its off-the-shelf gene edited CAR-T cell therapy.

Photo: Rachel Haurwitz, president and CEO of Caribou Biosciences

These initial ANTLER phase 1 data are scheduled to be shared at the European Hematology Association 2022 Hybrid Congress, being held in Vienna, Austria, June 9-17, 2022.

“Our initial CB-010 data are exciting, and we believe these results show the potential to set a new therapeutic bar in treating patients with aggressive r/r B-NHL (relapsed or refractory B cell non-Hodgkin lymphoma),” said Rachel Haurwitz, president and CEO of Caribou Biosciences. “These excellent initial outcomes represent important steps toward validating our chRDNA genome-editing platform as well as our plans for future development of CB-010 and our broader pipeline,” said Rachel Haurwitz, president and CEO of Caribou Biosciences.

CB-010 is the first allogeneic anti-CD19 CAR-T cell therapy in the clinic with a PD-1 knock-out, a genome-editing strategy designed to limit premature CAR-T cell exhaustion, potentially leading to better tumor debulking and an improved therapeutic index through sustained antitumor activity. Caribou said its goal is to develop CB-010 such that it will meaningfully rival autologous cell therapies to reach broader groups of patients globally who are in need of off-the-shelf treatments.

CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology to insert a CD19-specific CAR into the TRAC gene and knock out PD-1 to boost the persistence of antitumor activity. CB-010 is the first allogeneic CAR-T cell therapy in the clinic with a PD-1 knock out.

The data to be presented includes safety, tolerability, and initial antitumor activity of CB-010 administered at dose level 1 (40×10⁶ CAR-T cells) to 6 patients with r/r B-NHL who had relapsed after previous treatment with a median of 3 prior therapies (range 2-8). Prior to a single dose of CB-010, patients received a lymphodepletion regimen consisting of cyclophosphamide at 60 mg/kg/d for 2 days followed by fludarabine at 25 mg/m2/d for 5 days.

As of the February 23, 2022 data cutoff date, 6 patients had been treated with CB-010 and 5 had completed the 28-day dose-limiting toxicity (DLT) evaluation period. 100 percent (n=5) achieved a response; 80 percent (n=4) achieved a complete response, and 20 percent (n=1) achieved a partial response. All 4 patients who achieved a CR at 28 days had an ongoing CR at 3 months. The longest measured CR as of the data cutoff date was 6 months.

Following treatment with CB-010, there were no cases of graft versus host disease. 3 of 6 patients developed Grade 3 or 4 adverse events (AEs) within the first 28 days: neutropenia (50 percent), thrombocytopenia (33 percent), anemia (17 percent), and hypogammaglobulinemia (17 percent). One patient experienced Grade 1 CRS (17 percent) and Grade 3 ICANS (17 percent), which was characterized as a DLT, for which the patient received tocilizumab and steroids and recovered from the DLT within 39 hours. This patient went on to achieve a CR.

Based on promising initial safety and efficacy data from cohort 1 at dose level 1 (40×10⁶ CAR-T cells), the ANTLER trial is now enrolling patients in cohort 2 at dose level 2 (80×10⁶ CAR-T cells). Additional data are expected by year end.

“We believe this initial level of activity is unparalleled for a single, starting dose of cell therapy,” said Syed Rizvi, chief medical officer of Caribou. “CB-010 was generally well-tolerated with adverse events routinely observed in autologous or allogeneic anti-CD19 CAR-T cell therapies. At EHA next month, we are scheduled to share longer follow up data from the patients in Cohort 1 who received a single administration of CB-010 at the first dose level.”

Author: Rare Daily Staff