A2B530 Earns FDA Orphan Drug Designation in CEA+ Colorectal Cancer

The safety and efficacy of treatment with A2B530 will be evaluated in patients with CRC, pancreatic cancer, and non–small cell lung cancer (NSCLC) as part of the phase 1/2 EVEREST-1 study (NCT05736731), which is currently open for enrollment.

The FDA has granted orphan drug designation to novel cell therapy A2B530 as a treatment for patients who are germline heterozygous HLA-A*02 positive and have colorectal cancer (CRC) expressing carcinoembryonic antigen (CEA) that has lost HLA-A*02 expression, according to a press release from A2 Biotherapeutics, Inc.¹

Developers designed the autologous logic-gated cell therapy using the proprietary Tmod^TM platform, which makes use of a dual receptor that attacks malignant cells while protecting normal cells. The agent includes an activator that targets CEA as well as a blocker that is directed towards HLA-A*02.

“The FDA granting orphan drug designation validates the tremendous unmet need for improved therapies for patients with [CRC],” William Go, MD, PhD, chief medical officer at A2 Biotherapeutics, said in the press release.¹ “This designation supports our commitment to use our novel technology platform to develop new treatment options for patients with difficult-to-treat cancers.”

The safety and efficacy of treatment with A2B530 will be evaluated in patients with CRC, pancreatic cancer, and non–small cell lung cancer (NSCLC) as part of the phase 1/2 EVEREST-1 study (NCT05736731), which is currently open for enrollment. Patients will receive a preconditioning lymphodepletion regimen plus a single dose of A2B530 autologous logic-gated Tmod T cells intravenously.

The trial’s primary end points are adverse effects (AEs), dose-limiting toxicities, and the recommended phase 2 dose (RP2D) in the phase 1 portion.² The primary end point of the phase 2 portion is overall response rate (ORR) based on independent central review using RECIST v1.1 guidelines. Secondary end points include the presence of A2B520 as assessed via polymerase chain reaction tests and cytokine analysis.

Patients with histologically confirmed recurrent, unresectable, locally advanced or metastatic CRC, NSCLC, pancreatic cancer, or other solid tumors related to CEA expression and measurable lesions of more than 1.0 cm per CT imaging are able to enroll on the trial. Additional eligibility criteria include having adequate organ function, an ECOG performance status of 0 to 1, and a life expectancy of at least 3 months. Additionally, those who enroll on the EVEREST-1 trial must have their T cells collected as part of the pre-screening BASECAMP-1 study (NCT04981119).

Those with disease not suitable for management with local therapy or standard-of-care therapy that is therapeutic and not palliative are unable to enroll on the trial. Patients are also unsuitable for enrollment if they have prior allogenic stem cell transplant; prior solid organ transplant; unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within 6 months of entry; new symptomatic pulmonary embolism or deep vein thrombosis within 3 months of entry; or require supplemental home oxygen.

Developers previously announced that the first patient had received a dose of study treatment as part of EVEREST-1 in May 2023.³

“We believe the selectivity of the Tmod platform forms the foundation for a new class of therapeutics for solid tumor cancers, with the goal of killing tumors while avoiding the dose-limiting toxicities associated with well-known cancer targets,” Scott Foraker JD, president and chief executive officer at A2 Biotherapeutics, said in a press release at the time dosing for the first patient was completed.³ “Dosing our first patient is a significant milestone for A2 Bio and for patients seeking novel treatment options. This is the first medicine of an innovative pipeline that leverages the selectivity provided by the blocker to provide potentially safer and more efficacious therapeutics for [patients with] cancer.”

References

1. A2 Bio receives FDA orphan drug designation for novel cell therapy program A2B530 in colorectal cancer. News release. A2 Biotherapeutics, Inc. March 4, 2024. Accessed March 5, 2024. https://tinyurl.com/4bu8kc5x
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. February 2, 2024. Accessed March 5, 2024. https://www.clinicaltrials.gov/study/NCT05736731
3. A2 Bio announces first patient dosed in phase 1 clinical trial of A2B530, a novel cell therapy for the treatment of colorectal, pancreatic and non-small cell lung cancers. News release. A2 Biotherapeutics, Inc. May 30, 2023. Accessed March 5, 2024. https://tinyurl.com/5n87jkkp