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Allogeneic CAR T Yields 15-Month CR in Follicular Lymphoma

The first 6 patients dosed in the ANTLER trial had a 50% CR rate at 6 months.

A patient treated with the chimeric antigen receptor (CAR) T-cell therapy CB-010 (Caribou Biosciences) for their relapsed or refractory aggressive B cell non-Hodgkin lymphoma (r/r B-NHL) has maintained a complete response (CR) after 15 months.1

This case report from the phase 1 ANTLER trial (NCT04637763) was presented at the Lymphoma, Leukemia, & Myeloma Congress, held in New York City, New York on October 18-22, 2022, by John L. Harcha, MD, hematologist/oncologist and chief resident, Oncology Hematology Care, The Jewish Hospital, Cincinnati, OH.

“The 15-month CR for the first patient in the ANTLER trial exceeded our expectations at this initial dose level and we are highly encouraged by this outcome as we aim to set a new therapeutic bar for patients with relapsed or refractory B-NHL,” Rachel Haurwitz, PhD, president and chief executive officer, Caribou Biosciences, said in a statement.2

The patient is a 66-year-old man who was diagnosed in 2013 with aggressive follicular lymphoma that progressed within 24 months. The patient had received 8 prior lines of therapy. After treatment with 40x106 CB-010 cells, he had a CR at day 23, which has been maintained at 15 months of evaluation.In the first 6 patients dosed there was a 100% CR rate which fell to 50% at 6 months after treatment.

READ MORE: Allogeneic CAR-T Begins Phase 2 Clinical Trial

No graft-versus-host disease (GvHD), cytokine release syndrome, or immune effector cell associated neurotoxicity syndrome (ICANS) were observed in the first patient. The patient did have grade 3 sepsis from E. coli infection and grade 3 C. difficile infection after lymphodepletion but prior to CB-010 infusion and had a full recovery. Altogether, CB-010 was well-tolerated in the first 6 patients dosed, although there was 1 case of grade 3 ICANS.

“There is a significant unmet need for an allogeneic cell therapy that can rival the efficacy of autologous cell therapies. We believe that the safety and efficacy profile of CB-010 at dose level 1 has laid the foundation for the promise of this off-the-shelf cell therapy to meet that patient need. As we continue enrollment in the ANTLER trial, our goal is to build upon this foundation by assessing CB-010’s safety and durability at a higher dose level,” Haurwitz added.2

CB-010 is the first allogeneic anti-CD19 CAR T-cell therapy of its kind, engineered with a PD-1 knockout to improve antitumor activity and improve cell persistence by limiting CAR-T cell exhaustion. The knockout is achieved using the next-generation CRISPR-Cas9 technology chRDNA that significantly reduces off-target editing. The TRAC gene is also knocked out to eliminate T-cell receptor expression to reduce the risk of GvHD and a CD19-specific CAR is inserted into the TRAC locus.

The ANTLER trial is now enrolling patients at the second dose level of 80x106 CAR-T cells based on the initial safety and efficacy data. Additional data from the first cohort will be shared by the end of 2022.

REFERENCES
1. Harcha JL, Hart D, Chant K, et al. CRISPR-edited Allogeneic Anti-CD19 CAR-T Cell Therapy with PD-1 Knockout Induces Prolonged Complete Response in Relapsed/Refractory Follicular Lymphoma Patient: Case Report from CB-010 ANTLER Trial. Presented at: Lymphoma, Leukemia, & Myeloma Congress 2022, October 18-22, New York City, NY.
2. Caribou Biosciences presents case report on long-term follow up of first patient dosed in phase 1 ANTLER trial at the Lymphoma, Leukemia, & Myeloma Congress 2022. News release. Caribou Biosciences. October 18, 2022. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-presents-case-report-long-term-follow-first