Tasquinimod (DB05861): A Comprehensive Report on a Pleiotropic TME-Modulating Agent from Prostate Cancer Failure to Hematological Repurposing

1.0 Executive Summary

Tasquinimod (DB05861) is an orally active, investigational small molecule belonging to the quinoline-3-carboxamide class. It represents a second-generation analogue developed from the immunomodulatory agent roquinimex, engineered to possess a more favorable therapeutic index. The compound is distinguished by a novel, pleiotropic mechanism of action that does not directly target cancer cells but instead modulates the tumor microenvironment (TME) through dual inhibition of key pathological pathways. This unique mode of action, which encompasses immunomodulatory, anti-angiogenic, and anti-metastatic properties, has positioned Tasquinimod as a subject of significant clinical interest and strategic re-evaluation over its development history.

The clinical development of Tasquinimod is a story of stark contrast. Initially developed for solid tumors, it demonstrated considerable promise in a large, randomized Phase II trial for metastatic castration-resistant prostate cancer (mCRPC), where it significantly prolonged progression-free survival (PFS) compared to placebo.[1] These compelling results prompted a broad partnership between Active Biotech and Ipsen and led to the initiation of a large-scale, global Phase III trial (10TASQ10) designed to confirm its efficacy and establish an overall survival (OS) benefit.[3] The trial successfully met its primary endpoint, once again demonstrating a statistically significant improvement in radiographic PFS (rPFS). However, it critically failed to confer any benefit in OS, the key secondary endpoint, ultimately revealing an unfavorable risk-benefit profile in this patient population. This outcome led to the discontinuation of the entire prostate cancer development program in 2015.[5]