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Highlights from the 2025 American Society of Clinical Oncology Annual Meeting |
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| The Impact of DNA Repair Genetic Alterations Identified by Circulating Tumor DNA on Sensitivity to Radium-223 in Bone mCRPC |
| Steven Blinka, MD, PhD |
| Steven Blinka presented a prospective phase 2 trial evaluating whether DNA damage repair (DDR) gene alterations identified by circulating tumor DNA predict sensitivity to radium-223 in bone metastatic castration-resistant prostate cancer. The study hypothesizes that mCRPC patients with DDR alterations may derive greater benefit from radium-223, given its mechanism of inducing double-strand DNA breaks. Early enrollment is underway, aiming to assess response rates, survival outcomes, and the role of germline vs. somatic alterations in radium-223 efficacy. |
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| FLEX-MRT: A Randomized Phase 2 Trial of Flexible and Extended Dosing of 177Lu-PSMA-617 Molecular Radioligand Therapy in mCRPC |
| Adrien Holzgreve, MD |
| Adrien Holzgreve presented the FLEX-MRT trial, a randomized phase 2 study evaluating flexible, response-based extended dosing (up to 12 cycles) of ¹⁷⁷Lu-PSMA-617 versus standard fixed dosing (6 cycles) in men with mCRPC. The trial aims to determine whether a tailored approach can improve 2-year survival, with early imaging and PSA response guiding treatment holidays and restarts. Currently recruiting, the trial seeks to optimize efficacy and safety of PSMA-targeted radioligand therapy. |
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| A Randomized, Open-Label, Phase 2b Study of the Bromodomain Inhibitor ZEN-3694 + Enzalutamide versus Enzalutamide in Patients with mCRPC |
| Rahul R. Aggarwal, MD |
| Rahul Aggarwal presented a phase 2b randomized trial evaluating ZEN-3694, a bromodomain inhibitor, plus enzalutamide versus enzalutamide alone in patients with mCRPC who progressed on abiraterone. The study focuses on patients with poor response to prior androgen receptor inhibitors, hypothesizing that the combination may overcome AR-independent resistance. The primary endpoint is radiographic progression-free survival, with about 150 of 200 planned patients enrolled to date. |
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| SECuRE: A Dose Escalation/expansion Study to Assess the Anti-Tumor Efficacy of 67Cu-SAR-bisPSMA in Patients with mCRPC |
| Geoffrey B. Johnson, MD, PhD |
| Geoffrey Johnson presented the SECuRE trial, a Phase I/IIa study evaluating the safety and anti-tumor efficacy of 67Cu-SAR-bisPSMA in patients with mCRPC, leveraging its dual PSMA-binding design for enhanced tumor targeting. Early data suggest improved uptake and promising preclinical efficacy compared to single-target agents. The trial includes dose escalation and expansion phases, with up to four treatment doses, and a subset receiving combination therapy with enzalutamide. |
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| ProstACT Global: A Phase 3 Study of 177Lu-Rosptamab + Standard of Care Versus Standard of Care Alone in Patients with mCRPC |
| Scott T. Tagawa, MD, MS, FACP, FASCO |
| Scott Tagawa presented ProstACT Global, a Phase 3 trial evaluating 177Lu-rosopatamab combined with standard of care versus standard of care alone in patients with PSMA-positive mCRPC. This study includes a dosimetry and safety lead-in followed by a randomized expansion to assess radiographic progression-free survival and overall survival, targeting patients who have progressed after prior hormonal and taxane therapies. The trial aims to improve treatment specificity and outcomes by using targeted radioimmunotherapy with 177Lu-rosopatamab. |
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| PSMA-DC: An Open-Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 Versus Observation in Patients with Metachronous PSMA-Positive Oligometastatic Prostate Cancer |
| A. Oliver Sartor, MD |
| Oliver Sartor presented PSMA-DC, a phase 3 trial comparing 177Lu-PSMA-617 versus observation in patients with metachronous PSMA-positive oligometastatic prostate cancer after stereotactic body radiation therapy (SBRT). The study aims to delay metastasis and the need for androgen deprivation therapy by assessing metastasis-free survival, time to next hormonal therapy, and other progression and quality of life endpoints in about 450 patients. |
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| TRIPLE-SWITCH (SWOG/CCTG-PR26): A Randomized Phase III Clinical Trial for the Addition of Docetaxel to Androgen Receptor Pathway Inhibitors in Patients with mCSPC and Suboptimal PSA Response |
| Michael Ong, MD, FRCPC |
| Michael Ong presented TRIPLE-SWITCH (SWOG/CCTG-PR26), a phase III trial investigating whether adding docetaxel to ARPIs improves overall survival in mCSPC patients with suboptimal PSA response after initial ADT and ARPI therapy. This international randomized study enrolls 830 patients and compares standard ADT + ARPI versus the addition of docetaxel, aiming to address poor prognosis in patients showing PSA ≥0.2 ng/mL at 6–12 months despite therapy. |
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| ARASTEP: Darolutamide + ADT in Patients with High-Risk Biochemical Recurrence of Prostate Cancer: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study |
| Alicia K. Morgans, MD, MPH |
| Alicia Morgans presented ARASTEP, a phase 3 randomized, double-blind trial evaluating darolutamide plus ADT versus placebo plus ADT in patients with high-risk biochemical recurrent prostate cancer who have PSMA PET/CT-positive lesions but no metastases on conventional imaging. The study aims to improve radiological progression-free survival, with secondary endpoints including metastasis-free survival, time to castration resistance, and overall survival. |
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