CAR T-Cell Therapy A2B530 Receives Orphan Drug Designation for the Treatment of Colorectal Cancer

A2B530 (A2 Biotherapeutics), a CAR T-cell therapy, has received Orphan Drug Designation for the treatment colorectal cancer that expresses carcinoembryonic antigen (CEA) and has lost HLA-A*02 expression in patients with germline heterozygous HLA-A*02(+) disease, according to a news release.¹

Investigators hypothesize that the autologous logic-gated cell therapy can target tumor cells but protect healthy tissue because it has an intrinsic self-regulating safety switch that can reduce damage to healthy tissue. This hypothesis will be evaluated in the phase 1/2 EVEREST-1 (NCT05736731) trial.²

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“The FDA granting Orphan Drug Designation validates the tremendous unmet need for improved therapies for patients with colorectal cancer,” said William Go, MD, PhD, chief medical officer of A2 Bio, in the press release. “This designation supports our commitment to use our novel technology platform to develop new treatment options for patients with difficult-to-treat cancers.”¹

The multi-center, open-label, phase 1/2 EVEREST-1 study aims to evaluate A2B530 for the treatment of solid tumors in colorectal cancer, pancreatic cancer, and non-small cell lung cancer, among other types of solid tumors expressing CEA and no HLA-A*02 expression. Patients in the EVEREST-1 study were initially part of the BASECAMP-1 (NCT04981119) study, during which their T cells were collected, processed, and stored for future use.²

The primary end point of the phase 1 trial is obtaining optimal dose and safety. The primary end point of the phase 2 trial is continued safety and efficacy—the efficacy of the recommended dose at killing solid tumor cells and protecting healthy cells.¹

Colorectal cancer (a combined term for colon and rectal cancers) occurs when polyps (clumps of cell growth) occur in the colon or rectum and eventually become cancerous. Common risk factors include older age, Black race, personal or family history of polyps or cancer, inflammatory bowel disease, genetics, diabetes and obesity, typical Western diet, and smoking and alcohol use.³

The most common treatments for colorectal cancer include surgery, radiation, targeted therapy, and immunotherapy;³ however, many of the current therapies for this cancer and others with solid tumors can be fatal for patients.²

Study investigators suggest that this CAR T-cell therapy is more safe than previous targeted therapies—the CAR T-cells not only eradicates the tumor cells but do so without harming healthy cells because they contain an intrinsic safety switch to reduce damage to healthy tissue.²

REFERENCES

1. A2 Bio Receives FDA Orphan Drug Designation for Novel Cell Therapy Program A2B530 in Colorectal Cancer. A2 Biotherapeutics, Inc. News Release. March 4, 2024. Accessed on March 5, 2024. https://www.businesswire.com/news/home/20240304501299/en

2. A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Subjects With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression (EVEREST-1). ClinicalTrials.gov. Study Record. Last updated on February 2, 2024. Accessed on March 5, 2024. https://www.clinicaltrials.gov/study/NCT05736731

3. Colon Cancer. Mayo Clinic. Article. Accessed on March 5, 2024. https://www.mayoclinic.org/diseases-conditions/colon-cancer/symptoms-causes/syc-20353669