Patients with metastatic castration-resistant prostate cancer face a tough battle. Their cancer has spread and standard treatments no longer work. This early trial tested a new drug called EC1169. It is a small molecule that targets a specific protein on cancer cells and delivers a powerful anti-cancer agent. The team also used a matching imaging agent to see the drug at work. They compared these new tools against standard computed tomography and bone scans. The results showed the new imaging agent found more bone lesions than the old methods. This means doctors could see the disease more clearly. The drug also seemed to help patients whose cancer cells showed less activity at the start. These patients lived longer without their cancer spreading compared to others. However, the drug showed limited activity overall. This is common in early-stage research where scientists are just learning if a new approach works. Safety was not a major concern in this small group of 103 people. The study highlights the need to test both the drug and the imaging tools together in future trials. This combination could help doctors spot the disease earlier and track how well it responds to treatment.
EC1169 and 99mTc-EC0652 show increased bone lesion detection and longer rPFS in mCRPC patientsA new prostate cancer drug shows promise but has limited activity in this early trial
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Key Takeaway
Note limited activity of EC1169 in this Phase I study of mCRPC patients.
This Phase I study enrolled 103 patients with metastatic castration-resistant prostate cancer. The population consisted of patients with mCRPC. The setting was not reported. The intervention involved EC1169, a PSMA-targeted small molecule conjugated to a tubulysin analog warhead, and 99mTc-EC0652, a PSMA imaging agent. The comparator was standard scans including computed tomography and bone scans. The follow-up duration was 2.9 months.
Main results showed increased sensitivity for detecting bone lesions compared with standard scans. The absolute numbers for this outcome were not reported. For radiographic progression-free survival, longer duration was observed in patients with a decrease in PSMA-positive CTCs at baseline versus C3D1. The effect size was 8 versus 2.9 months. The p-value was P = 0.04. Other secondary outcomes included PSMA-positive CTCs and association with response and PSMA imaging.
Safety and tolerability data were not reported. No adverse events, serious adverse events, or discontinuations were reported. The study limitations noted that EC1169 showed limited activity. The certainty of the evidence is low because this is a Phase I study. Practice relevance highlights the importance of assessing both PSMA-based CTC and imaging assays in future validation trials.
What this means for you:
Early testing shows a new prostate cancer drug and imaging agent detect lesions better than standard scans. More on Metastatic Castration Resistant Prostate Cancer
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View Original Abstract ↓
PURPOSE: Prostate-specific membrane antigen (PSMA)-directed therapies provide meaningful clinical benefit in metastatic castration-resistant prostate cancer (mCRPC), yet responses remain limited, underscoring the need for additional biomarkers of PSMA expression heterogeneity. In this study, we explored the relationship between PSMA imaging and PSMA expression on circulating tumor cells (CTC) in our early-phase trial using a PSMA-targeted small molecule.
EXPERIMENTAL DESIGN: This phase I study investigated EC1169, a small molecule conjugated to a tubulysin analog warhead, and 99mTc-EC0652, a PSMA imaging agent. Part A (dose escalation) identified the recommended phase II dose. Part B (dose expansion) assessed radiographic progression-free survival (rPFS) as its primary endpoint. We enrolled and treated 103 patients with mCRPC. Most part B patients underwent 99mTc-EC0652 PSMA imaging. A CTC assay assessed PSMA-positive CTCs and their association with response and PSMA imaging.
RESULTS: 99mTc-EC0652 single-photon emission computed tomography (SPECT) imaging demonstrated increased sensitivity for detecting bone lesions compared with standard scans (computed tomography/bone scans). Using an optimized CTC assay, we observed that patients with a decrease in PSMA+ CTCs at baseline versus C3D1 displayed a longer rPFS (8 vs. 2.9 months; P = 0.04). Importantly, patients with predominantly PSMA-positive disease on 99mTc-EC0652 imaging also harbored PSMA-negative CTCs, with a subset displaying neuroendocrine prostate cancer-like morphology.
CONCLUSIONS: Although EC1169 showed limited activity, CTC and imaging analyses showed significant heterogeneity in PSMA expression on CTCs in patients with predominantly PSMA-positive lesions on SPECT. Our study highlights the importance of assessing both PSMA-based CTC and imaging assays in future validation trials.
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