At an efficacy data cutoff date of September 29, 2025, a single dose of partially matched (4 or more matched HLA alleles) vispa-cel generated an overall response rate (ORR) of 82%, comprising a 64% complete response (CR) rate for patients prospectively enrolled in the study’s partial HLA matching confirmatory cohort (n = 22). The 12-month progression-free survival (PFS) rate in this cohort was 51% (95% CI, 25%-70%); the median PFS was not reached (NR; 95% CI, 2.0-not evaluable [NE]), as was the median duration of response ([DOR] 95% CI, 1.7-NE). The median follow-up for the confirmatory cohort was 6.0 months.
Among patients who received vispa-cel with an optimized profile (n = 35), the ORR was 86% including a CR rate of 63%. The 12-month PFS rate was 53% (95% CI, 34%-69%) and the median PFS was NR (95% CI, 2.8-NE). The median DOR was also NR (95% CI, 2.1-NE). The median follow-up for the optimized profile cohort was 11.8 months. Of note, the longest responding patient, who completed the 2-year ANTLER trial and enrolled in the long-term follow-up study, has maintained a CR 3 years after infusion.
Collectively, these data show that the efficacy and durability of vispa-cel is commensurate with that of approved autologous CAR T-cell therapies, according to Caribou Biosciences, the drug’s developer.
“The ANTLER data mark an exciting advancement for the field of cellular immunotherapy,” Mehdi Hamadani, MD, a professor of medicine and section chief of hematologic malignancies at the Medical College of Wisconsin, and an investigator on the ANTLER trial, stated in a news release. “This clinical dataset demonstrates vispa-cel’s efficacy and durability are comparable to autologous CAR T[-cell] therapies, yet its off-the-shelf availability and favorable tolerability profile make it well suited for outpatient administration at both large academic centers and sophisticated community hospitals. This combination of robust clinical activity and accessibility could significantly broaden patient access to transformative CAR T-cell treatments, particularly for those who cannot wait or are ineligible for transplantation or autologous CAR T-cell therapies.”
How was the ANTLER trial designed?
ANTLER is a first-in-human, multicenter, open-label study evaluating the safety, emerging efficacy, pharmacokinetics and immunogenicity of vispa-cel in adult patients with a documented diagnosis of relapsed/refractory B-cell NHL.2
The study comprises two parts: a standard dose escalation (part A) with sequential, prespecified, increasing doses of vispa-cel and a dose-expansion portion (part B) where patients will receive vispa-cel at the dose determined in part A. Patients in both parts will receive vispa-cel following lymphodepletion, which consists of cyclophosphamide at 60 mg/kg/day for 2 days followed by fludarabine at 25 mg/m2/day for 5 days.1,2
The incidence of dose-limiting toxicities and the ORR with vispa-cel serve as the primary end points for parts A and B, respectively.2
As of the safety data cutoff date of September 2, 2025, the ANTLER trial had enrolled 84 patients, including a confirmatory cohort of 22 patients with CD19-naive large B-cell lymphoma (LBCL) in the second line.1 The confirmatory cohort was designed to prospectively confirm outcomes from partial HLA matching observed in prior retrospective analyses. Patients in the confirmatory cohort received vispa-cel at the recommended phase 2 dose (RP2D) of 80 × 10⁶ CAR T cells.
Leveraging a large clinical dataset of more than 140 patients dosed with allogeneic CAR T cells across multiple trials, 2 key factors were linked to successful patient outcomes: donor age (young vs older donors) and partial HLA matching (matching 2 or more alleles vs less than 2).
The optimized profile vispa-cel was manufactured from young donor-derived T cells, and the 35 patients matched a minimum of 2 HLA alleles with the T-cell donor. Twenty of the 35 patients in the optimized profile cohort were enrolled in the confirmatory cohort, and the remaining 15 patients were enrolled in the dose escalation or expansion.
What should be known about the safety profile of vispa-cel?
Regarding safety, vispa-cel was generally well tolerated among all patients treated in ANTLER (n = 84). At the safety data cutoff date, the most common any-grade treatment-emergent adverse effects in at least 25% patients included thrombocytopenia (62%), cytokine release syndrome (CRS; 55%), anemia (52%), neutropenia (39%), hypokalemia (26%), and leukopenia (26%).
In the overall patient population, the incidence of any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) was 14% (5% in the confirmatory cohort; 3% in the optimized cohort). Any-grade infections were observed in 51% of patients (41%; 57%).
Immune effector cell–associated hemophagocytic lymphohistiocytosis was reported in 2% of patients (5%; 3%), all of which were grade 3 or higher. Less than 5% of patients experienced grade 3 or higher CRS events in the overall patient population (5%; 3%). Notably, no instances of graft-vs-host disease or grade 3 or higher ICANS were observed in the confirmatory or optimized profile cohorts, although the latter was reported in 5% of patients in the overall patient population.
Prolonged cytopenias of grade 3 or higher were reported in 28% of 80 available patients in the overall patient population; among patients in the confirmatory (n = 19) and optimized (n = 32) cohorts, these rates were 26% and 22%.
What’s next for vispa-cel?
Of note, the FDA previously granted vispa-cel regenerative medicine advanced therapy, orphan drug, and fast track designations for B-NHL.
Enrollment for a small cohort (n = 5) of patients with LBCL in the third line who have been previously exposed to CD19-targeted therapy has been paused to concentrate efforts on the CD19-naive population. Moving forward, Caribou Biosciences plans to pursue a randomized, controlled pivotal phase 3 clinical trial, as recommended by the FDA. This trial will evaluate vispa-cel in approximately 250 CD19-naive patients with LBCL who are ineligible for both transplant and autologous CAR T-cell therapy.
Patients will receive either a single dose of vispa-cel at the RP2D following lymphodepletion or investigator's choice of standard chemoimmunotherapy. PFS will serve as the primary end point, and secondary end points will include ORR, CR, DOR, duration of CR, overall survival, quality of life, and safety. An interim analysis of PFS is planned.
“We believe that with these results, Caribou has achieved what the field has long sought—strong evidence that an allogeneic CAR T-cell therapy can be on par with the efficacy and durability of autologous treatments and broaden access with a safety profile that allows for outpatient use,” Rachel Haurwitz, PhD, Caribou’s president and chief executive officer, concluded. “This milestone positions vispa-cel as a potentially best-in-class allogeneic CAR T-cell therapy for patients with LBCL. We believe we have a straightforward regulatory path toward full registration by following the FDA’s recommendation for a randomized, controlled phase 3 trial in second-line LBCL, and we plan to refine our pivotal trial design in the coming months through continued engagement with the FDA.”
References
- Caribou Biosciences announces positive data from ANTLER phase 1 trial demonstrating efficacy and durability of vispa-cel (CB-010), an allogeneic CAR-T cell therapy, on par with autologous CAR-T cell therapies. News release. Caribou Biosciences. November 3, 2025. Accessed November 4, 2025. https://investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-positive-data-antler-phase-1-trial
- CRISPR-edited allogeneic anti-CD19 CAR-T cell therapy for relapsed/refractory B cell non-Hodgkin lymphoma (ANTLER). ClinicalTrials.gov. Updated March 24, 2025. Accessed November 4, 2025. https://clinicaltrials.gov/study/NCT04637763
