Advancements in Cancer Therapy: The Potential of ABBV-621 as a Novel TRAIL-Receptor Agonist

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein that can trigger cell death in cancer cells by binding to specific receptors. It has been considered a promising treatment for cancer due to its ability to induce apoptosis. However, resistance mechanisms have been identified, such as changes in receptor levels, overproduction of certain proteins that prevent cell death, and activation of alternative signaling pathways that promote cell survival.

ABBV-621 is a new TRAIL receptor agonist that is designed to enhance receptor clustering and does not rely on Fcγ-R-mediated crosslinking for its effects. It has shown to be effective in inducing cell death in various types of cancer cells and has demonstrated potent antitumor activity in animal models. ABBV-621 has a favorable pharmacokinetic profile and has been well-tolerated in preclinical toxicity studies.

A phase 1/1b clinical trial is planned to assess the safety, tolerability, and pharmacokinetics of ABBV-621 in patients with advanced solid tumors and hematologic malignancies. The study will also explore biomarkers for target engagement and clinical activity.

The findings were presented at the American Association for Cancer Research Annual Meeting in 2017, highlighting ABBV-621 as a potential best-in-class TRAIL-receptor agonist for treating various types of cancer.