(UroToday.com) The 2025 ASCO annual meeting featured a prostate cancer trials in progress session and a presentation by Dr. Scott T. Tagawa discussing ProstACT Global, a phase 3 study of 177Lu-rosptamab + standard of care versus standard of care alone in patients with metastatic castration-resistant prostate cancer (mCRPC). The treatment of advanced prostate cancer is challenging, with undesirable side effects that impact patient quality of life. Radioimmunotherapy can localize therapy to specific tumor cells in multiple organs to reduce or eliminate damage to normal tissue. The cell surface glycoprotein PSMA is an ideal therapeutic target as it is highly expressed by malignant prostate cells. There is a strong rationale for further investigation of the 177Lu-labeled, chelator-conjugated antibody, 177Lu-rosopatamab, as a potential first-line radioimmunotherapy candidate for the treatment of prostate cancer. Key differences between 177Lu-rosopatamab and 177Lu-vipivotide are highlighted in the following table:
This multinational, multicenter, prospective, randomized, open label phase 3 study will have 2 parts: a dosimetry and safety lead-in (n = 30) and a randomized treatment expansion (n = 490). In Part 1, patients will be divided into 3 groups (n = 10 each) to receive two single IV injections of 76 millicuries (mCi) each, 14 days apart, of 177Lu-rosopatamab with best standard of care combinations with abiraterone, enzalutamide, or docetaxel to fully characterize biodistribution and safety profiles of 177Lu-DOTA-rosopatamab + standard of care combinations. Standard of care received will be determined prior to treatment with 177Lu-rosopatamab. In Part 2, patients will be enrolled in a 2:1 ratio to receive either the best standard of care or two single IV injections of 76 mCi each (equivalent to a 45 mCi/m2 dose in a standard 1.7m2 individual) of 177Lu-rosopatamab, given 14 days apart, plus best standard of care. Standard of care will be determined prior to randomization, and a change in planned standard of care will not be permitted:
Eligible patients must have PSMA-expressing mCRPC that have progressed despite prior therapy with either enzalutamide or abiraterone plus prednisone, and one line of prior taxane therapy or have refused or are ineligible for taxanes. Patients must have adequate organ function, including at least 150x109/L platelets, hemoglobin 10 g/dL, and have PSMA-positive disease on 68Ga-PSMA-11 PET/CT imaging as confirmed by a central reader.
Key exclusion criteria include: (i) small cell histology, (ii) increased risk of hemorrhage or bleeding, (iii) known brain or hepatic metastases, (iv) history of stroke, (v) seizure, or (vi) treatment with radioisotopes within 6 months prior to randomization. The primary endpoint is radiographic progression-free survival, and a key secondary endpoint is overall survival. Additional secondary endpoints include 5-year overall survival, tumor objective response rate, time to symptomatic skeletal event, and health-related quality of life. This study is currently enrolling.
Presented by: Scott T. Tagawa, MD, MS, FACP, FASCO, Weill Cornell Medical College of Cornell University, New York, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.