Allogeneic CAR-T CB-010 Produces Durable Responses Among Patients With R/R B-NHL

Caribou Biosciences’ CB-010, an allogeneic CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, has produced durable responses among patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) who were treated in the phase 1 ANTLER clinical trial (NCT04637763).¹

Among 16 patients who were treated with CB-010 as of the June 20, 2023, efficacy data cutoff date the overall response rate (ORR) was 94% (n = 15) and the complete response (CR) rate was 69% (n = 11). Furthermore, 7 patients (44%) had CRs at 6 months posttreatment or later and 1 patient’s CR has been maintained for 24 months and remains ongoing. Among a subset of 10 patients with large B-cell lymphoma (LBCL), the ORR was 90% (n = 9), the CR rate was 70% (n = 7), and 5 patients (50%) had CRs at 6 months posttreatment or later. In this subset, 1 patient’s CR has been maintained for 18 months and remains ongoing.

In terms of safety, Caribou reported that CB-010 was generally well-tolerated and demonstrated a safety profile consistent with autologous or allogeneic CD19-directed CAR-T therapies. As of the May 4, 2023, safety data cutoff date, 7 of the 16 patients (44%) had experienced cases of cytokine release syndrome (CRS) and 4 of the 16 patients (25%) had experienced cases of immune effector cell-associated neurotoxicity syndrome (ICANS). Two patients treated at the study’s lowest dose-level (40x10⁶ CAR T-cells) had cases of ICANS that were grade 3 or higher, but both cases fully resolved with supportive care. There were no grade 3 or higher cases of CRS. Infections were reported in 7 patients (44%) in the trial; 1 patient (6%) had an infection that was grade 3 or higher. None of the patients in the study experienced graft-versus-host disease. Thrombocytopenia, neutropenia, and anemia were among the most common adverse events reported. Grade 3 or higher cases of thrombocytopenia occurred in 69% of patients, grade 3 or higher cases of neutropenia occurred in 56% of patients, and grade 3 or higher cases of anemia occurred in 50% of patients. One dose-limiting toxicity has been reported in a patient treated at the study’s lowest dose-level.

“I am excited to see the initial and durable response rates for patients following a single dose of CB-010 in the ANTLER Phase 1 clinical trial,” Loretta J. Nastoupil, MD, the deputy chair and associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center and an investigator on the ANTLER trial, said in a statement.¹ “The data are promising and may offer a clinical advantage as an off-the-shelf option compared with approved autologous CAR-T cell therapies. In addition to encouraging antitumor activity, CB-010 could provide greater access to patients, including those who are not eligible for or cannot wait for an autologous CAR-T cell therapy. As the field of cell therapy moves to earlier lines of treatment, I look forward to being part of CB-010’s development as an off-the-shelf treatment option for patients with LBCL in the second-line clinical setting.”

The patient population in ANTLER includes 7 patients with diffuse LBCL, 1 patient with primary mediastinal LBCL, 2 patients with follicular lymphoma (FL), 2 patients with high-grade B cell lymphoma, 3 patients with mantle cell lymphoma, and 1 patient with marginal zone lymphoma. It was noted that the 2 patients with FL had disease that was aggressively behaving with progression of disease within 24 months. The number of prior lines of therapy received by the patients ranged from 1 to 8; the 4 patients who only received 1 prior line of therapy had disease that was primary refractory. Patients in ANTLER were treated with CB-010 at 3 dose-levels: 40x10⁶ CAR T-cells, 80x10⁶ CAR T-cells, and 120x10⁶ CAR T-cells.

“CB-010 dose escalation data rival the responses from autologous cell therapies and demonstrate the potential utility of an off-the-shelf CAR-T cell therapy that could, if approved, provide greater access to patients in need,” Rachel Haurwitz, PhD, the president and chief executive officer of Caribou Biosciences, added to the statement.¹ “We are actively enrolling patients in dose expansion to gain a better understanding of the safety and antitumor activity of CB-010 in a greater number of patients. We look forward to determining a recommended phase 2 dose of CB-010, engaging with the FDA on next steps, and reporting ANTLER dose expansion data in the first half of 2024.”

This interim data update is the latest in a series of positive updates reported by Caribou Biosciences as of late. On July 6, 2023, the company announced that it had received a $25 million equity investment from Pfizer and added Sriram Krishnaswami, PhD, the vice president and development head for Multiple Myeloma at Pfizer Oncology’s Global Product Development division, to its Scientific Advisory Board.² Earlier, in March, 2023, Caribou reported that it had initiated the dose-expansion portion of ANTLER and that the first patient had been dosed in its phase 1 CaMMouflage clinical trial (NCT05722418) evaluating CB-011, an allogeneic antiBCMA CAR-T therapy, for the treatment of r/r multiple myeloma.³ Both CB-010 and CB-011 have received fast track designation from the FDA, in November 2022 and April 2023 respectively.^4,5 CB-010 also received regenerative medicine advanced therapy designation for the treatment of r/r LBCL in November 2022.

REFERENCES
1. Caribou Biosciences reports positive clinical data from dose escalation of CB-010 ANTLER phase 1 trial in r/r B-NHL. News release. Caribou Biosciences, Inc. July 13, 2023. Accessed July 14, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-reports-positive-clinical-data-dose
2. Caribou biosciences announces $25 million equity investment from Pfizer. News release. Caribou Biosciences, Inc. July 6, 2023. Accessed July 14, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-25-million-equity-investment
3. Caribou Biosciences announces dosing of first patient in the CaMMouflage phase 1 trial of CB-011, an allogeneic anti-BCMA CAR-T cell therapy for the treatment of relapsed or refractory multiple myeloma. News release. Caribou Biosciences, Inc. March 29, 2023. Accessed July 14, 2023.https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-dosing-first-patient-cammouflage
4. Caribou Biosciences announces the FDA granted regenerative medicine advanced therapy (RMAT) and fast track designations to CB-010, an allogeneic anti-CD19 CAR-T cell therapy. News release. Caribou Biosciences. November 29, 2022. Accessed July 14, 2023.https://www.globenewswire.com/news-release/2022/11/29/2564105/0/en/Caribou-Biosciences-Announces-the-FDA-Granted-Regenerative-Medicine-Advanced-Therapy-RMAT-and-Fast-Track-Designations-to-CB-010-an-Allogeneic-Anti-CD19-CAR-T-Cell-Therapy.html
5. Caribou Biosciences announces FDA granted fast track designation to CB-011, an allogeneic CAR-T cell therapy for relapsed or refractory multiple myeloma. News release. Caribou Biosciences. April 4, 2023. Accessed July 14, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-fda-granted-fast-track-designation