Study launches of 225Ac-PSMA-Trillium in mCRPC

Dosing has commenced in a phase 1 study (NCT06217822) evaluating the safety, tolerability, and initial efficacy of the targeted alpha therapy ²²⁵Ac-prostate-specific membrane antigen (PSMA)-Trillium in patients with metastatic castration-resistant prostate cancer (mCRPC), announced Bayer, the developer of the therapy, in a news release.¹

Primary completion of the phase 1 study is expected in 2027.

“Despite recent advances in the treatment landscape for prostate cancer, there is still a high unmet need for novel precision therapy options to improve outcomes for patients with metastatic castration-resistant prostate cancer. ²²⁵Ac-PSMA-Trillium is a novel approach, which could provide a new treatment to address this unmet need in mCRPC,” said Fred Saad, MD, FRCS, in the news release.¹ Saad is a professor and the chairman of surgery at the University of Montreal as well as the director of genitourinary oncology at the University of Montreal Hospital Center in Canada.

In total, the phase 1 study plans to enroll 118 patients with advanced mCRPC.² The goals of the study are to assess the therapy’s safety, tolerability, and initial efficacy, as well to determine a recommended dose level for phase 2 of the study.

Participants included in the trial will receive ²²⁵Ac-PSMA-Trillium once every 4 weeks for up to 6 treatment cycles. Each patient will be followed in the study for up to 6 years, which comprises a screening period of up to 30 days, 6 months of treatment, and follow-up for up to 60 months following the end of treatment.

The primary outcome measures for the study are the incidence of treatment-emergent adverse events (TEAEs), the severity of TEAEs, the incidence of dose-limiting toxicities, objective response rate, PSA50 response rate (defined as at least a 50% decline in PSA value from baseline), and overall PSA response. Secondary outcome measures include radiographic progression-free survival, duration of response, and duration of PSA50 response.

Substudies conducted during the dose escalation/dose expansion phases of the trial will explore the clearance of radioactivity from the body over time, the doses of radiation that are delivered to normal organs and tumors, and the ability of an experimental agent, Tris-POC, to decrease the amount of radiation absorbed by the normal organs.

²²⁵Ac-PSMA-Trillium is a next-generation targeted alpha therapy that is labeled with actinium-225 and comprises a novel PSMA-targeting small molecule with a customized albumin-binding moiety. According to the company, ²²⁵Ac-PSMA-Trillium is designed to potentially improve therapeutic efficacy while reducing toxicity to normal organs such as the salivary glands.

Preclinical data on ²²⁵Ac-PSMA-Trillium was presented at the 2024 American Association for Cancer Research Annual Meeting in San Diego, California, highlighting the in vitro and in vivo characterization of the therapy.³ Data showed that in prostate cancer models, 225Ac-PSMA-Trillium induced strong tumor growth inhibition.

“Targeted radionuclide therapy is a strategic pillar of precision oncology at Bayer, holding the promise to shift the treatment paradigm for patients, including those whose disease has developed resistance to other treatments,” said Dominik Ruettinger, MD, PhD, head of research and early development for oncology at Bayer, in the news release.¹ “We are excited to announce initiation of the phase I and dosing of the first patient with ²²⁵Ac-PSMA-Trillium. With its unique design, we believe it could offer a meaningful benefit for patients with metastatic prostate cancer, and we look forward to advancing the program through clinical development.”

Primary completion of the phase 1 study is expected in 2027.

References

1. Bayer starts phase I study with novel targeted radionuclide therapy 225Ac-PSMA-trillium in advanced metastatic prostate cancer. News release. Bayer. May 15, 2024. Accessed May 17, 2024. https://www.bayer.com/media/en-us/bayer-starts-phase-i-study-with-novel-targeted-radionuclide-therapy-225ac-psma-trillium-in-advanced-metastatic-prostate-cancer/

2. First-in-human study of 225Ac-PSMA-Trillium (BAY 3563254) in participants with advanced metastatic castration-resistant prostate cancer (mCRPC) (PAnTHA). ClinicalTrials.gov. Last updated May 1, 2024. Accessed May 17, 2024. https://www.clinicaltrials.gov/study/NCT06217822

3. Preclinical evaluation of an actinium-225 labeled PSMA-targeting small molecule (225Ac-PSMA-Trillium (BAY 3563254)) for the treatment of metastatic castration resistant prostate cancer (mCRPC). Presented at: 2024 American Association for Cancer Research Annual Meeting. April 5 – 10, 2024. San Diego, California. Abstract 6033