CRISPR Clinical Trial Update: Caribou Reports Positive Phase 1 Results for Blood Cancer Candidate CB-010

Earlier this week, Caribou Biosciences reported new 12-month clinical data from cohort 1 in the ongoing ANTLER Phase 1 trial of CB-010 for relapsed/refractory B cell non-Hodgkin lymphoma (r/r B-NHL). The latest data demonstrates long-term durability following a single infusion of CB-010 at the initial dose level 1 (40x10⁶ CAR-T cells).

CB-010 is a CRISPR-edited off-the-shelf allogeneic anti-CD19 CAR-T cell candidate, and data released in June 2022 revealed 100% complete response rates as best response, following a single dose at the initial dose level in patients with aggressive r/r B-NHL. Based on this data, CB-010 became the first allogeneic CAR-T cell therapy to achieve 100% CR.

The data released this week revealed that 6 out of 6 patients in cohort 1 achieved a CR as best response, 3 of 6 patients maintained a durable CR at 6 months, and 2 of 6 patients maintain a long-term CR at the 12-month scan and remain on the ANTLER trial. The company also reported 18 months as the longest CR maintained to date in the ANTLER trial, and this was achieved by the first patient dosed with CB-010. CB-010 was generally well tolerated with adverse events consistent with autologous or allogeneic anti-CD19 CAR-T cell therapies.

First PD-1 knockout CAR-T candidate to enter clinical trial

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.

Dosing continues and new data expected in 2023

Caribou reported last month that based on promising initial clinical data so far, the U.S. Food and Drug Administration (FDA) has granted CB-010 both Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations. The company also shared in its press release this week that it has observed an encouraging safety profile for CB-010 at dose level 2 (80x10⁶ CAR-T cells) with no dose-limiting toxicities in the 3 patients treated so far. Enrolment is ongoing for patients at dose level 3 (120x10⁶ CAR-T cells). The company expects to provide an ANTLER trial update in 2023.

Read all of our coverage on Caribou Biosciences here.

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

This article was published on 14th December 2022. The article was amended on 15th December 2022 to reflect clinical data released in June 2022.