EVEREST-1 Trial in Solid Tumors Doses First Patient With A2B530


The autologous CAR T-cell therapy A2B530 is being investigated for solid tumors in the multicenter, first-in-human, phase 1/2 EVEREST-1 study.

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

J. Randolph Hecht, MD

A2 Biotherapeutics has announced that the first patient with solid tumors has been dosed with the autologous chimeric antigen receptor (CAR) T-cell therapy A2B530 in the first-in-human, multicenter phase 1/2 EVEREST-1 study (NCT05736731).1

The CAR-T therapy was developed by leveraging the clinical-stage cell therapy company’s Tmod platform—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 and its dual-receptor design allows for the selective elimination of CEA-expressing cancer cells that have permanently lost the HLA-A*02 gene.

Scott Foraker, chief executive officer of A2 Biotherapeutics, Inc., said in a statement that the company believes that the selectivity of their 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." He added that the first patient dosing marks "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.”

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, said in a recent interview with OncLive®, “I’m very excited about both BASECAMP-1 and EVEREST-1," expressing particular excitement 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.”

To qualify for participation in EVEREST-1, patients must first enroll in the noninterventional, observational BASECAMP-1 study (NCT04981119). In BASECAMP-1, investigators are seeking to examine how often solid tumors lose HLA using next-generation sequencing (NGS).3 Apheresis will be performed on patients to collect and store T cells. Upon disease progression, those who meet eligibility requirements will be screened for EVEREST-1, and their T cells will be used to produce A2B530 for administration.

Currently, EVEREST-1 is enrolling patients with recurrent unresectable, locally advanced, or metastatic CEA-expressing solid tumors—this includes those with colorectal cancer, pancreatic cancer, and non–small cell lung cancer.4 The 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.

Exclusion criteria include prior allogeneic stem cell transplant or solid organ transplant, as well as receipt of cancer treatment within 3 weeks of cell therapy infusion. Receipt of radiotherapy within 28 days of study treatment is also not permitted.

EVEREST-1's coprimary end points for the first phase of the trial include examination the rate of adverse events and dose-limiting toxicities for each dose level and the determination of the recommended phase 2 dose of A2B530. In the second phase of the trial, the primary end point is to assess the overall response rate achieved with the therapy.

As of now, 10 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.

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
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