Caribou’s CRISPR-Edited CAR T-Cell Therapy CB-010 Elicits Complete Response in R/R B-NHL

CB-010, an allogeneic chimeric antigen receptor (CAR) T cell therapy in development by Caribou Biosciences, produced a 100% overall response rate (ORR) in all 5 patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) who received the therapy in the ANTLER phase 1 trial (NCT04637763).

The company announced initial results in a statement¹ ahead of a presentation at the upcoming European Hematology Association (EHA) 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. 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,” Rachel Haurwitz, PhD, Caribou’s president and chief executive officer, said in the statement.

The ANTLER trial is evaluating the safety, tolerability, and efficacy of CB-010, an allogeneic anti-CD19 CRISPR-edited CAR T-cell therapy that is engineered to knock out PD-1, intended to help improve antitumor activity. The 2-part trial consists of a dose escalation phase that follows at 3+3 design, followed by a dose expansion phase in which participants will receive the dose indicated in phase 1. The primary end points are number of dose-limiting toxicities over 28 days post-infusion and tumor response, as measured by objective response rate, over 12 months. The study plans to enroll up to 50 participants.

The current data account for 6 patients with r/r B-NHL with a history of a median of 3 prior therapies who were administered CB-010 at dose level 1 (40x10⁶ CAR-T cells) following a lymphodepletion regimen of cyclophosphamide at 60 mg/kg/d for 2 days followed by fludarabine at 25 mg/m2/d for 5 days. As of the cutoff date, all 6 patients had been treated and 5 had completed 28-day follow-up.

At that point, 4 patients achieved a complete response and 1 achieved a partial response. Notably, all 4 patients who had a complete response sustained that response at 3 months, with the longest recorded complete response as of the data cutoff being 6 months.

In terms of safety, no cases of graft versus host disease were reported, with 3 of 6 patients developing grade 3 or 4 adverse events within the 28-day follow-up period, including neutropenia (50%), thrombocytopenia (33%), anemia (17%), and hypogammaglobulinemia (17%). One patient experienced grade 1 cytokine release syndrome and grade 3 immune effector cell-associated neurotoxicity syndrome, a dose-limiting toxicity. The patient received treatment and recovered within 39 hours, going on to achieve a complete response.

Based on these data, trial investigators are now enrolling the second cohort of patients at dose level 2 (80x10⁶ CAR-T cells).

“We are slated to present additional ANTLER interim data at EHA next month and expect more data by year end as we continue to advance our lead program. Our overarching 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,” Haurwitz said.

REFERENCE

Caribou Biosciences announces positive initial data for cb-010 anti-cd19 allogeneic car-t cell therapy. News release. Caribou Biosciences. May 12, 2022. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-positive-initial-data-cb-010-anti