2. Academic Validation
  3. Correlative Biomarker Analysis of PSMA Expression on CTCs and PSMA Imaging in a Phase I Study of PSMA Targeted Tubulysin Conjugate EC1169

Correlative Biomarker Analysis of PSMA Expression on CTCs and PSMA Imaging in a Phase I Study of PSMA Targeted Tubulysin Conjugate EC1169

  • Clin Cancer Res. 2026 Jan 27. doi: 10.1158/1078-0432.CCR-25-2313.
Samir Zaidi 1,  Phillip H Kuo 2,  Tiago Paiva Prudente 3,  Kristine P Lacuna 4,  Hani M Babiker 5,  Renan Aparicio 6,  Joseph D Schonhoft 7,  Luisa Fernandez 8,  Richard Messmann 9,  Michael Groaning 10,  Anthony W Tolcher 11,  Michael S Gordon 12,  Don C Yoo 13,  Ulka Vaishampayan 14,  Joel Picus 15,  Daniel P Petrylak 16,  Oliver Sartor 17,  Michael J Morris 18
Affiliations

Affiliations

  • 1 Yale Cancer Center New Haven, CT United States.
  • 2 City of Hope United States.
  • 3 Universidade Federal de Goiás Goiânia Brazil.
  • 4 Memorial Sloan Kettering Cancer Center New York, NY United States.
  • 5 Mayo Clinic Jacksonville, Florida United States.
  • 6 Rockefeller University United States.
  • 7 Tagworks Pharmaceuticals (Netherlands) Boston, MA United States.
  • 8 Epic Sciences (United States) San Diego, CA United States.
  • 9 Amgen (United States) Cambridge, MA United States.
  • 10 Amgen (United States) United States.
  • 11 South Texas Accelerated Research Therapeutics San Antonio, TX United States.
  • 12 HonorHealth Scottsdale, AZ United States.
  • 13 Brown University United States.
  • 14 University of Michigan-Ann Arbor Ann Arbor, Michigan United States.
  • 15 Washington University in St. Louis St Louis, MO United States.
  • 16 Yale Cancer Center New Haven, Connecticut United States.
  • 17 Tulane University New Orleans, MN United States.
  • 18 Memorial Sloan Kettering Cancer Center New York, New York United States.
PMID: 41591990 DOI: 10.1158/1078-0432.CCR-25-2313
Abstract

Purpose: 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. Here, we explored the relationship of PSMA imaging and PSMA expression on circulating tumor cells (CTCs) in our early phase trial using a PSMA-targeted small molecule.

Patients and methods: This Phase 1 study investigated EC1169, a small molecule conjugated to tubulysin analog warhead, and 99mTc-EC0652, a PSMA imaging agent. Part A (dose-escalation) identified the recommended phase 2 dose. Part B (dose-expansion) assessed radiographic progression-free survival (rPFS) as its primary endpoint. We enrolled and treated 103 mCRPC patients. Most Part B patients underwent 99mTc-EC0652 PSMA imaging. A CTC assay assessed for PSMA-positive CTCs and their association with response and PSMA imaging.

Results: 99mTc-EC0652 SPECT imaging demonstrated increased sensitivity for detecting bone lesions compared with standard scans (CT/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 (8.0 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 NEPC-like morphology.

Conclusions: While 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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-181696
    PSMA 显像剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z