The FDA granted fast track designation to a novel combination therapy for metastatic castration-resistant prostate cancer (mCRPC), pairing a first-in-class deoxycytidine kinase (dCK) inhibitor with a radioligand therapy targeting prostate-specific membrane antigen (PSMA).

This designation aims to accelerate development and review of treatments for serious conditions with unmet needs, offering hope for patients with advanced prostate cancer that no longer responds to hormone therapy. The radioligand therapy, already approved in 2022, delivers targeted radiation to PSMA-positive cancer cells, which are prevalent in over 80% of prostate cancer cases.  The dCK inhibitor, currently in phase 1 trials, targets the nucleoside salvage pathway, a process cancer cells rely on for DNA synthesis. By blocking dCK, the inhibitor disrupts the supply of DNA precursors, making cancer cells more vulnerable to the DNA-damaging effects of the radioligand therapy.

This synergy is the rationale behind the combination: the inhibitor enhances the radioligand’s ability to kill cancer cells, potentially improving outcomes for patients who have exhausted options like androgen receptor inhibitors or taxane-based chemotherapies.

Early phase 1 trial data show the dCK inhibitor is well-tolerated, with no dose-limiting toxicities across doses from 40 mg to 320 mg daily, and five of 19 patients achieved stable disease.

The approach leverages precision oncology, using PSMA as a biomarker to identify eligible patients and deliver targeted treatment. Ongoing trials will further evaluate the combination’s safety and efficacy, with the goal of offering a new lifeline to those battling this aggressive disease.

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