Based on promising data from the dose-escalation portion of the phase 1 ANTLER trial evaluating CB-010 in patients with B-cell non-Hodgkin lymphoma, the dose-expansion portion has initiated enrollment.
Treatment with CB-010, an allogeneic anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) was generally well-tolerated with a safety profile consistent with autologous or allogeneic anti-CD19 CAR-T cell therapies.1
These findings are long-term follow-up data from the dose-escalation portion of the phase 1 ANTLER trial (NCT04637763), which included 16 patients with multiple subtypes of aggressive R/R B-NHL treated with CB-010 at 3 dose levels (40x106, 80x106, and 120x106 CAR-T cells) As of the data cutoff date, there were no dose-limiting toxicities (DLTs) seen at dose levels 2 or 3, and a single DLT at dose level 1. The overall response rate (ORR) was 94% in 15 of 16 following a single dose of CB-010. A total of 69% of patients (n = 11) achieved a complete response (CR), and 44% of patients (n = 7) had a CR at ≥6 months. To date, the longest CR is 24 months.
Among a subset of 10 patients with large B cell lymphoma (LBCL), the ORR was 90% ORR (n = 9) with 70% (n = 7) of patients achieving a CR. Half of the patients (n = 5) had a CR at ≥6 months with 18 months being the longest CR maintained to date.
Trial Name: A Phase 1, Multicenter, Open-Label Study of CB-010, a CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy in Patients With Relapsed/Refractory B Cell Non-Hodgkin Lymphoma (ANTLER)
ClinicalTrials.gov Identifier: NCT04637763
Sponsor: Caribou Biosciences, Inc.
Recruitment Contact: Socorro Portella, MD, 973-866-7567, SPortella@CaribouBio.com
Completion Date: Septemeber 2025
Additionally, the most common adverse events (AEs) that were grade 3 or higher were thrombocytopenia (69%), neutropenia (56%), and anemia (50%). Any grade treatment-emergent adverse events (TEAEs) of special interest reported among the 16 patients included cytokine release syndrome (CRS; 44%), immune effector cell–associated neurotoxicity (ICANS; 25%) and infections (44%). Grade 3 or greater TEAEs were seen in patients, including ICANS (13%) and infections (6%).
"Having an off the shelf allogeneic CAR T cell therapy that is well tolerated and can result in durable responses is desirable to improve access to cellular therapy. There are a number of allogeneic cellular therapies are under exploration and are at various stages of development. What is intriguing about CB-010 is the CRISPR technology utilized for gene engineering allows for efficient ways to modify allogeneic T cells from healthy donors and this product in particular explores PD-knockout [KO] to address one mechanism of resistance," Loretta J. Nastoupil, MD, deputy chair and associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston and investigator on the ANTLER trial, told Targeted Oncology. The other potential differentiating factor is the lymphocyte depleting chemotherapy which is higher than auto CAR trials, though previously explored. The enhanced lymphodepleting chemotherapy may also help the allo CARs evade the immune system at least in the short term. Persistence has been a limitation of the allo CARs under development and whether it is the lymphodepleting chemotherapy or the PD-1 KO that makes the preliminary results from CB-010 intriguing is unclear, but warrants further study. A larger sample size will help further explore the early signal that appears promising."
Supported by these positive data, second-line patients with LBCL are now being enrolled in the ongoing dose-expansion portion of the ANTLER clinical trial where the mid dose and the high dose from escalation (80x106 and 120x106 CAR-T cells) are being evaluated in approximately 30 second-line patients. Investigators aim to determine the recommended phase 2 dose (RP2D), and then additional patients may enroll in the trial.
Initial data from the dose-expansion portion of the trial are expected to be reported in the first half of 2024.
“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. 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,” added Nastoupil.
ANTLER is a first-in-human, phase 1, multicenter, open-label trial evaluating the safety and efficacy of CB-010 in adult patients with R/R B-NHL.2 The study is made up of 2 parts, including a dose-escalation portion (part A), and a dose-expansion portion (part B). In the part A, a 3 + 3 design will be followed with sequential, prespecified, increasing doses. Here, patients with R/R NHL will receive CB-010 following lymphodepletion. Part B will then administer CB-010 to patients at the determined dose from part A.
Patients aged 18 years and older at the time of enrollment with a documented diagnosis of relapsed or refractory NHL after they have received prior standard of care are eligible to enroll in the study if they have an ECOG performance status of 0 or 1 and adequate hematologic, renal, liver, cardiac, and pulmonary organ function.
The primary end point of part A is the incidence of AEs defined as DLTs with onset within 28 days after CB-010 infusion, and the primary end point for part B is ORR with a time frame of up to 12 months.
“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,” said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer, in the press release.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.”
