Caribou Biosciences Cleared to Evaluate Allogeneic CAR-T CB-010 in Lupus

Mehdi Hamadani, MD
Credit: Medical College of Wisconsin

Caribou Biosciences has received clearance from the FDA of an investigational new drug (IND) application for the evaluation of CB-010, its investigational allogeneic CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, in lupus nephritis (LN) and extrarenal lupus (ERL).¹

In light of the IND clearance, Caribou stated that it anticipates initiating its planned phase 1 GALLOP clinical trial (NCT identifier pending) for CB-010 in patients with LN and ERL by the end of 2024. The open-label, multicenter study will evaluate a single dose level of CB-010, which will be delivered as a single infusion following a cyclophosphamide and fludarabine conditioning regimen. Notably, participants will receive CB-010 manufactured from donors with partial human leukocyte antigen (HLA) matching, with the intention of achieving better clinical outcomes.

“The human leukocyte antigen, or HLA, system acts as our body’s identity card to know one’s ‘self’ from ‘not self’,” Mehdi Hamadani, MD, a professor of medicine and section chief of hematologic malignancies at Medical College of Wisconsin, said in a statement.¹ “In stem cell transplants, it has been shown that a close HLA match between patients and donors significantly reduces the rejection of the therapy. This same logic can be applied to allogeneic CAR-T cells as well, so that the activity of the therapy persists long enough to target and destroy the diseased cells.”

CB-010 was originally developed for the treatment of hematologic malignancies and is currently being evaluated in patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) in the ongoing phase 1 ANTLER clinical trial (NCT04637763).² In July 2023, Caribou reported efficacy and safety data from the dose-escalation portion of ANTLER. In terms of efficacy, the company noted that in 16 patients who had been treated as of a June 20,2023 data cutoff, the overall response rate was 94% (n = 15) and the complete response rate was 69% (n = 11). In terms of safety, the company stated 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 and 4 of the 16 patients (25%) had experienced cases of immune effector cell-associated neurotoxicity syndrome.

“Intriguing data from the ongoing ANTLER trial support incorporating an HLA matching strategy into Caribou’s CB-010 trials, an innovative clinical approach that can potentially improve outcomes for patients,” Hamadani, who is also an investigator for ANTLER, continued.¹ “I am pleased to be part of the ANTLER trial to advance the development of CB-010 as an off-the-shelf CAR-T cell therapy that aims to address the limitations of currently approved treatment options.”

Alongside the announcement of the IND clearance for lupus, Caribou noted that ANTLER is continuing to enroll patients with large B-cell lymphoma in the second-line setting and that it expects to report data from the dose-expansion portion of that trial at a medical congress during the second quarter of 2024.¹ CB-010 has previously received regenerative medicine advanced therapy, fast track, and orphan drug designations from the FDA for r/r B-NHL.

CB-010 is one of 4 cell therapies that Caribou is currently developing for cancer indications.³ In addition to a CAR natural killer cell therapy aimed at solid tumors, CB-020, which remains in the discovery phase of preclinical development, the company has 2 other allogeneic CAR-T therapies in clinical development for the treatment of hematological malignancies: CB-012 and CB-011. Notably, in October 2023, CB-012, which is directed at C-type lectin-like molecule-1, received clearance of an IND application for a trial in r/r acute myeloid leukemia. CB-011, a BCMA-targeted CAR-T intended to treat r/r multiple myeloma, is being evaluated in the phase 1 CaMMouflage trial (NCT05722418), which dosed its first participant in March 2023.⁴

REFERENCES
1. Caribou Biosciences expands clinical development of CB-010 with FDA clearance of IND in lupus. News release. Caribou Biosciences, Inc. April 4, 2024. Accessed April 8, 2024. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-expands-clinical-development-cb-010-fda
2. 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
3. Caribou Biosciences. Pipeline. Website. Accessed October 26, 2023. https://www.cariboubio.com/pipeline/
4. 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 October 26, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-dosing-first-patient-cammouflage