CB-010 Elicits 94% ORR in Relapsed/Refractory Non-Hodgkin Lymphoma

Loretta J. Nastoupil, MD

The allogeneic CAR T-cell therapy CB-010 demonstrated early signs of durable antitumor activity and favorable safety in patients with relapsed/refractory B-cell non-Hodgkin lymphoma, according to extended follow-up data from the dose-escalation portion of the phase 1 ANTLER trial (NCT04637763).

Among 16 patients treated in dose escalation, all of whom had received at least 2 prior lines of chemoimmunotherapy or had primary refractory disease, the overall response rate was 94% (n = 15), and 69% (n = 11) achieved complete response (CR). More than half of patients who achieved CR (44%; n = 7) maintained their response for at least 6 months, with the longest CR reaching 2 years.

In the subset of patients with large B-cell lymphoma (LBCL; n = 10), 90% (n = 9) achieved an objective response, 70% (n = 7) experienced CR, and 50% (n = 5) maintained their CR for 6 months or more, with the longest CR reaching 18 months.

CB-010 was generally well tolerated with adverse effects (AEs) similar to other autologous or allogeneic anti-CD19 CAR T-cell therapies. No dose-limiting toxicities (DLTs) occurred at dose levels 2 or 3 following 1 DLT at dose level 1.

In light of these data, Caribou has opened the dose-expansion portion of the trial to patients with LBCL in need of second-line therapy. In this portion, the mid and high doses from the escalation phase, 80 x 10⁶ and 120 x 10⁶, will be evaluated in approximately 30 patients to establish the recommended phase 2 dose, after which additional patients may be enrolled. To date, 4 patients have been enrolled to this cohort, showing an ORR of 100% and CR rate of 50% (n = 2); both responses were maintained for at least 6 months, with the longest response reaching 1 year.

Preliminary data from the dose-expansion portion of the trial are expected 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,” 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, said in a press release.

“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,” Nastoupil added.

CB-010 is the first allogeneic anti-CD19 CAR T-cell therapy being developed for second-line treatment in patients with LBCL, according to Caribou Biosciences, and has received regenerative medicine advanced therapy, fast track, and orphan drug designations from the FDA. CB-010 is also the first allogeneic anti-CD19 CAR T-cell therapy designed with PD-1 knockout, allowing for enhanced antitumor activity by restricting premature CAR T-cell exhaustion.

In the escalation phase, three dose levels of CB-010 were evaluated: 40 x 10⁶, 80 x 10⁶, and 120 x 10⁶ CAR T cells.

Treatment-emergent AEs of special interest included cytokine release syndrome (grade 1/2, 44%), immune effector cell–associated neurotoxicity syndrome (grade 1/2, 25%; grade ≥3, 13%), and infections (grade 1/2, 44%; grade ≥3, 6%). The most frequent grade 3 or higher AEs included thrombocytopenia (69%), neutropenia (56%), and anemia (50%).

“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, president and chief executive officer of Caribou, said. “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.”

Reference

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. July 13, 2023. Accessed July 18, 2023. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-reports-positive-clinical-data-dose