FDA grants fast track designation to TRE-515 with 177Lu-PSMA-617 for mCRPC

The FDA has granted fast track designation for TRE-515 in combination with ¹⁷⁷Lu-PSMA-617 (lutetium Lu 177 vipivotide tetraxetan; Pluvicto) for the treatment of metastatic castration-resistant prostate cancer (mCRPC), developer Trethera Corporation reported in a news release.¹

The investigational treatment is being evaluated in phase 1 clinical trials for solid tumors.

Supporting the FDA’s decision were results from an in-human phase 1 trial in patients with cancer, “as well as a growing body of preclinical data, including findings presented at the American Association for Cancer Research annual meeting,” Trethera reported. The phase 1 study is evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of TRE-515 oral monotherapy in adults with advanced solid tumors. The company reports that the treatment has shown early evidence of antitumor activity as well a favorable safety profile; notably, an 18-fold dose escalation without limiting toxicities.

Jean DeKernion, MD

“Trethera is working closely with the FDA to accelerate development and reimagine cancer care by combining radioligand therapy with TRE-515 to extend the lives of patients with prostate cancer and elevate current standards of care,” said Jean DeKernion, MD, Trethera Director Emeritus and cofounder of the Specialized Program of Research Excellence in Prostate Cancer at the University of California, Los Angeles (UCLA).

TRE-515 is a first-in-class treatment that works by inhibiting deoxycytidine kinase, “the rate-limiting enzyme in the nucleoside salvage pathway, one of two biosynthetic pathways that generate DNA precursors. It is believed that some forms of cancer may be preferentially dependent on the salvage pathway to support tumor growth, and certain autoimmune diseases might also respond to TRE-515 treatment,” according to Trethera.

In the news release, Trethera Chairman and CEO Ken Schultz, MD, said, “This designation marks a critical milestone in our mission to develop more effective, well-tolerated therapies for aggressive and treatment-resistant prostate cancers. By combining TRE-515 with targeted radioligand therapy, we seek to accelerate precision medicine going beyond current standards of care and deliver meaningful, long-term benefits to patients.”

Added Michael Jung, MD, Distinguished UCLA Professor of Chemistry & Biochemistry, “I believe that TRE-515 has the potential to make a meaningful difference in the lives of [patients with] prostate cancer and I am pleased that Trethera has received this fast track designation to expedite development. The chemical structure of TRE-515 was designed for a specific, on-target, binding to create an optimal drug profile.”

In March 2022, the FDA approved ¹⁷⁷Lu-PSMA-617 for use in adult patients with mCRPC who have received prior treatment with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy. In March 2025, the agency approved an expanded indication to include patients with prostate-specific membrane antigen-positive mCRPC who have been treated with ARPI and are considered appropriate to delay taxane-based chemotherapy.²

REFERENCES

1. FDA grants fast track designation for TRE-515 in combination with radiation therapy for the treatment of metastatic castration resistant prostate cancer. News release. Trethera Corporation. July 9, 2025. Accessed July 9, 2025. https://www.globenewswire.com/news-release/2025/07/09/3112644/0/en/FDA-Grants-Fast-Track-Designation-for-TRE-515-in-Combination-with-Radiation-Therapy-for-the-Treatment-of-Metastatic-Castration-Resistant-Prostate-Cancer.html

2. FDA approves Novartis radioligand therapy Pluvicto for earlier use before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer. News release. Novartis Pharma AG. March 28, 2025. Accessed July 9, 2025. https://www.novartis.com/news/media-releases/fda-approves-novartis-radioligand-therapy-pluvicto-earlier-use-chemotherapy-psma-positive-metastatic-castration-resistant-prostate-cancer