Clinical Trial Update: Positive Initial Data for CRISPR-Edited CAR-T Therapy in Aggressive Blood Cancer

Caribou Biosciences recently announced positive initial clinical trial data for its gene-edited CAR-T cell therapy candidate CB-010. Caribou is developing CB-010 as an off-the-shelf allogeneic anti-CD19 CAR-T cell therapy for relapsed/refractory B cell non-Hodgkin lymphoma (r/r B-NHL).

CB-101 is being evaluated in the ANTLER Phase 1 trial, and the data released so far data revealed a 100% overall response rate (ORR, 5 of 5 patients) and an 80% complete response rate (CR, 4 of 5 patients) following a single dose at the initial dose level in patients with aggressive r/r B-NHL.

This data makes CB-010 the first allogeneic CAR-T cell therapy to achieve 100% ORR.

CRISPR-edited healthy donor T cells

CB-010 is Caribou’s most advanced cell therapy candidate and is derived from healthy donor T cells that are genome-edited using the company's next-generation CRISPR-Cas technology that is based on CRISPR hybrid RNA-DNA (chRDNAs).

Specfically, a CD19-specific CAR is inserted into the TRAC gene, which encodes the T cell receptor alpha constant. The PD-1 gene is also deleted in these cells. This gene encodes the PD-1 protein that functions as a safety switch on T cells that cancer cells turn on to protect themselves from T cell-mediated immune responses.

CB-010 is the first allogeneic CAR-T cell therapy with a CRISPR-mediated PD-1 deletion to be cleared for a clinical trial.

Positive initial data in aggresive B-cell non-Hodgkin lymphoma

The ANTLER trial is a Phase 1 clinical study to evaluate the safety, emerging efficacy, pharmacokinetics and immunogenicity of CB-010 in adults with r/r B-NHL after prior lymphodepletion therapy, which is a treatment that reduces the patient’s own T cell numbers, so they will not antagonise the proliferation of the infused engineered CAR-T cells.

The recent data announcement was made ahead of the European Hematology Association (EHA) 2022 Hybrid Congress (June 9-17, 2022), where Caribou Biosciences is scheduled to share the results for CB-010.

According to Caribou Bioscience's press relesase, six patients with r/r B-NHL who had relapsed after previous cancer treatments received a single dose of CB-010 (at dose level 1 (40x10⁶ CAR-T cells)), following a sequential lymphodepletion regimen consisting of cyclophosphamide and fludarabine. As of the data cutoff date, five of these patients had completed the 28-day dose-limiting toxicity (DLT) evaluation period. All five patients achieved a response; where four patients achieved a CR that was still ongoing at three months, and the fifth patient achieved a PR. The longest measured CR as of the data cutoff date was six months.

In relation to safety, no cases of graft versus host disease were observed following treatment with CB-010. Half of the patients treated developed Grade 3 or 4 adverse events (AEs) within the first 28 days, which included neutropenia, thrombocytopenia, anaemia, and hypogammaglobulinaemia. One patient experienced Grade 1 cytokine release syndrome (CRS) and Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS). This was characterised as a DLT that required treatment, and the patient recovered from the DLT within 39 hours and went on to achieve a CR.

Dosing continues and new data expected at end of 2022

Based on the promising initial safety and efficacy data so far, the ANTLER trial is now enrolling patients in cohort 2 at dose level 2 (80x10⁶ CAR-T cells). Additional data are expected by the end of 2022. The trial, which aims to enrol 50 adult participants, has an anticipated primary completion date in August 2025.

For a complete overview of current gene editing clinical trials, check out CRISPR Medicine News' Clinical Trials Database.