First Patient Dosed in EVEREST-1 Trial of A2B530 in Solid Tumors

J. Randolph Hecht, MD

The first patient has been dosed with the autologous CAR T-cell therapy A2B530 in the multicenter, first-in-human, phase 1/2 EVEREST-1 study (NCT05736731), according to an announcement from A2 Biotherapeutics, Inc.¹

A2B530 was developed by leveraging the clinical-stage cell therapy company’s Tmod platform, which is a logic-gated T-cell therapy platform. The product contains an activator that recognizes CEA and a blocker targeted against HLA-A*02.^1,2 The dual-receptor design allows for selective elimination of CEA-expressing cancer cells that have permanently lost the HLA-A*02 gene.

“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 dose-limiting toxicities [DLTs] associated with well-known cancer targets,” Scott Foraker, chief executive officer of A2 Biotherapeutics, Inc., stated in a press release. “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.”

To participate in EVEREST-1, patients must first enroll to the non-interventional, observational BASECAMP-1 study (NCT04981119), in which investigators are seeking to examine how often solid tumors lose HLA using next-generation sequencing (NGS).³ Apheresis will be performed on patients so that their T cells can be collected and stored. Upon disease progression, those who meet eligibility requirements will be screened for EVEREST-1, and their T cells will be used to produce A2B530.

EVEREST-1 is enrolling patients with recurrent unresectable, locally advanced, or metastatic CEA-expressing solid tumors, including colorectal cancer, pancreatic cancer, and non–small cell lung cancer.⁴ Notably, their tumors should demonstrate HLA-A*02 loss of heterozygosity by NGS.

Other eligibility criteria include having an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, acceptable organ function, and having previously received appropriate required treatment for their solid tumor.

Patients could not have previously undergone allogeneic stem cell transplant or solid organ transplant, nor could they have received cancer treatment within 3 weeks of cell therapy infusion. Receipt of radiotherapy within 28 days of study treatment was also not permitted.

The co-primary end points for the phase 1 portion of the trial include examining the rate of adverse effects and dose-limiting toxicities for each dose level and determining the recommended phase 2 dose of A2B530. The primary objective for the second phase of the trial is to assess the overall response rate achieved with the therapy.

“I’m very excited about both BASECAMP-1 and EVEREST-1,” said J. Randolph Hecht, MD, the director of the UCLA Gastrointestinal (GI) Oncology Program and a professor of clinical medicine at the David Geffen School of Medicine at UCLA, in a recent interview with OncLive®. “I am very excited about the biological model of having a blocker because I’m afraid that otherwise it’s going to be very difficult to do cellular therapies in solid tumors. If this is the secret sauce, if this is the mechanism to overcome [the difficulties], it opens up a lot of treatment strategies for our patients who desperately need them.”

Ten clinical sites are currently open and screening patients for EVEREST-1.1

BASECAMP-1 is also screening patients who may derive benefit from products like A2B530.

References

1. 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 June 1, 2023. https://www.a2bio.com/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/
2. Pipeline. A2 Biotherapeutics. Accessed June 1, 2023. https://www.a2bio.com/our-pipeline/#programs-a2b530
3. Solid tumor analysis for HLA loss of heterozygosity (LOH) and apheresis for CAR T- cell manufacturing (BASECAMP-1). ClinicalTrials.gov. Updated March 22, 2023. Accessed June 1, 2023. https://clinicaltrials.gov/ct2/show/NCT04981119
4. 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. Updated May 31, 2023. Accessed June 1, 2023. https://www.clinicaltrials.gov/ct2/show/NCT05736731