One-time treatment with vispa-cel (CB-010), Caribou Biosciences’ off-the-shelf CAR T-cell therapy candidate, resulted in durable responses in people with hard-to-treat large B-cell lymphoma (LBCL).
That’s according to data from the ongoing Phase 1 ANTLER clinical trial (NCT04637763), which is testing the therapy in adults with treatment-resistant or relapsed LBCL.
Vispa-cel, an allogeneic CAR T-cell therapy made using immune T-cells from healthy donors, was found to be equally effective as autologous CAR T-cell therapy, which uses a patient’s own T-cells. Because it was generally well-tolerated, vispa-cel may be eligible for administration in an outpatient setting.
“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 CEO, said in a company press release. “This milestone positions vispa-cel as a potentially best-in-class allogeneic CAR-T cell therapy for patients with large B-cell lymphoma.”
Meanwhile, the U.S. Food and Drug Administration (FDA) has recommended that Caribou launch a pivotal Phase 3 trial to test vispa-cel as a second-line therapy for LBCL patients who are ineligible for transplant and autologous CAR-T cell therapy. Pivotal studies are those designed to support a potential application for a therapy’s approval.
“We believe we have a straightforward regulatory path toward full registration by following the FDA’s recommendation for [an appropriately controlled] Phase 3 trial in second-line large B cell lymphoma, and we plan to refine our pivotal trial design in the coming months through continued engagement with the FDA,” Haurwitz said.
CAR T-cell therapy harnesses body’s own immune T-cells to fight cancer
CAR T-cell therapy harnesses the body’s own immune T-cells to fight cancer, including LBCL, a type of blood cancer that affects B-cells, the immune cells responsible for producing antibodies.
With vispa-cel, T-cells from healthy donors are engineered to produce a chimeric antigen receptor, or CAR, that specifically recognizes CD19, a protein found on the surface of B-cells. The modified T-cells, which are more effective at locating and destroying the targeted cancer cells, are then infused into the patient.
To ensure immune compatibility, allogeneic CAR T-cell therapy requires that the donor and patients match in terms of certain versions of HLA genes, which help the immune system distinguish the body’s own cells from foreign cells or invaders.
ANTLER enrolled 84 LBCL patients, including a confirmatory group of 22 participants who previously received a first-line treatment regimen but were naïve to anti-CD19 therapy. This group was designed to confirm the positive outcomes of partial HLA matching (at least four matched HLA alleles).
After a median follow-up of six months, 82% of people in this group had responded to treatment, 64% showed no signs of cancer, indicating a complete response, and 51% had no signs of cancer progression at one year.
Planned Phase 3 trial will assess progression-free survival
A group of 35 anti-CD19 therapy-naïve participants received vispa-cel with an optimized profile. The therapy in this group was manufactured from T-cells derived from a young healthy donor, and patients matched in at least two HLA alleles with the donor. Twenty patients in the optimized profile group were part of the confirmatory group.
After a median follow-up of nearly one year in the optimized profile group, a single dose of vispa-cel resulted in an overall response rate of 86% and a complete response rate of 63%. Also, 53% of patients had no signs of cancer progression at one year.
Those numbers are “numerically identical to the numbers we expect from FDA-approved autologous products,” Mehdi Hamadani, MD, professor of medicine at the Medical College of Wisconsin and ANTLER trial investigator, said in a company webcast.
The longest-responding patient in the optimized profile group, who completed the two-year ANTLER trial and is now enrolled in a long-term follow-up study (NCT05332054), continues to show no signs of cancer three years after vispa-cel treatment.
This clinical [data set] demonstrates vispa-cel’s efficacy and durability are comparable to autologous CAR-T 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.
The therapy was generally safe and well-tolerated. The most commonly reported adverse events were low platelet counts (62%), cytokine release syndrome (an inflammatory reaction; 55%), anemia (52%), low immune neutrophil counts (39%), low potassium levels (26%), and low immune cell counts (26%).
“This clinical [data set] demonstrates vispa-cel’s efficacy and durability are comparable to autologous CAR-T 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,” Hamadan said.
Caribou’s planned Phase 3 study of vispa-cel is expected to enroll up to 250 anti-CD19 therapy-naïve LBCL patients who are ineligible for transplant and autologous CAR-T cell therapy. Participants will be randomly assigned to receive either a single dose of vispa-cel or standard-of-care immunochemotherapy agents, as chosen by the investigator.
The main goal will be to assess progression-free survival, or the time a person lives without signs of cancer progression. Secondary goals include overall response rate, complete response rate, duration of response, overall survival, quality of life, and safety.
“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,” Hamadani said.
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