AdAPT-001 oncolytic adenovirus shows promising phase 1 cancer treatment results

Oncolytic adenoviruses have won significant attention in recent years as a novel approach to cancer treatment. One example of the trend is AdAPT-001 TGF-ß Trap, an engineered variant of the common cold virus equipped with a transforming growth factor-beta (TGF-β) “trap.” This mechanism is designed to latch onto and neutralize TGF-β, an immunosuppressive cytokine involved in cancer cell growth and disease progression.

At the 2023 ASCO Annual Meeting, the developer of AdAPT-001, EpicentRx, shared initial findings from a phase 1 trial on AdAPT-001. The initial data indicates that patients generally tolerate AdAPT-001 well.

So far, the study has enrolled 28 patients for treatment with AdAPT-001 as a single agent. EpicentRx plans to enroll an additional roughly 50 patients for a phase 2 portion where AdAPT-001 will be combined with immunotherapy.

In the phase 1 portion, the most common side effects were local inflammation, fever and fatigue. There were no reported instances of dose-limiting toxicities, grade 4 toxicities or treatment-related serious adverse events.

Phase 1 results for AdAPT-001 shared at the 2023 ASCO Annual Meeting

In a presentation at ASCO, the company highlighted encouraging signs of biological activity such as virus replication and tumor shrinkage. While some patients showed stable or progressive disease, others experienced durable stable disease for more than six months or demonstrated an ‘abscopal response,’ a systemic immune reaction that occurs when radiation therapy or another localized treatment not only reduces the size of a targeted tumor but also results in the shrinkage of untreated tumors elsewhere in the body.

Next steps for the AdAPT-001 cancer treatment candidate

Following the positive results, researchers plan to advance the compound to phase 2 trials, where it will be administered at a dose of 1.0 x 10¹² viral particles biweekly.

Dr. Anthony Paul Conley from the University of Texas MD Anderson Cancer Center in Houston, Texas led the study in partnership with a team of researchers from various research institutions. The trial began on March 29, 2021.

The phase 1 portion kicked off with a 3 + 3 dose escalation safety run-in design to gradually increase the dosage while monitoring patient safety. The trial then shifted into a dose expansion single-agent protocol, where researchers tested the drug as a standalone treatment. The trial concluded with an expansion single agent plus checkpoint inhibitor phase, exploring the potential synergistic effects of combining AdAPT-001 with a checkpoint inhibitor.

In recent years, there has been a growing amount of preclinical and clinical development of naturally occurring and genetically engineered oncolytic viruses, yielding encouraging data, as a recent article in Signal Transduction and Targeted Therapy noted. The promising results of the phase 1 AdAPT-001 study of an oncolytic adenovirus further underscore the potential of ongoing oncolytic virotherapy research for cancer treatment.