STEAP1 as a predictive biomarker for antibody-drug conjugate (ADC) activity in metastatic castration resistant prostate cancer (mCRPC).

Danila, Daniel C.; Fleisher, Martin; Carrasquillo, Jorge A.; Gilbert, Houston; Morris, Michael J.; Bellomo, Lawrence; Hendrikx, Petrus J.; Szafer-Glusman, Edith; Herkal, Amrita; Patel, Chintan; Schreiber, Nicole A.; Curtis, Kristen Rebecca; Maslyar, Daniel; Lemahieu, Vanessa; Fine, Bernard M.; Mamounas, Michael; Ungewickell, Alexander; Lackner, Mark R.; Scher, Howard I.; Kabbarah, Omar

doi:10.1200/jco.2015.33.15_suppl.5029

Cited by 4 publications

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“…Our objective was to generate a PET antibody tracer targeting STEAP1 to see if it could be used to assess STEAP1 expression, predict prognosis, and monitor response to anti-STEAP1 therapies. [ 89 Zr]Zr-DFO-MSTP2109A was chosen because this antibody has high affinity for STEAP1, has little cross-reactivity to normal tissues, and is internalized and ties in with a contemporaneous trial using an ADC based on the same antibody. ,, In our initial imaging report, we documented good localization of [ 89 Zr]Zr-DFO-MSTP2109A in bony sites of metastatic disease and although a limited number of patients had soft tissue disease, these sites were also visualized, including lesions in liver. All imaging-positive sites biopsied were positive histologically, suggesting that other imaging-positive sites also represented metastatic disease as described in our prior [ 89 Zr]Zr-DFO-MSTP2109A imaging report …”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Biodistribution of a [⁸⁹Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients

et al. 2019

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A six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a newly identified target in prostate cancer. The use of radio-labeled STEAP1-targeting antibodies with positron emission tomography (PET) may allow for detection of sites of metastatic prostate cancer and may refine patient selection for antigen-directed therapies. This was a prospective study in seven patients with metastatic castration-resistant prostate cancer who had at least one archival biopsy that was STEAP1-positive by immunohistochemistry. Patients received intravenous injections of ∼185 MBq and 10 mg of [89Zr]Zr-DFO-MSTP2109A, a humanized IgG1 monoclonal antibody directed against STEAP1. PET/CT images, blood samples, and whole-body counts were monitored longitudinally in six patients. Here, we report on safety, biodistribution, pharmacokinetics, dose estimates to normal tissues, and initial tumor targeting for this group of patients. There was no significant acute or subacute toxicity. Favorable biodistribution and enhanced lesion uptake (in both bone and soft tissue) were observed on imaging using a mass of 10 mg of DFO-MSTP2109A. The best lesion discrimination was seen at the latest imaging time, a median of 6 days postadministration. Pharmacokinetics showed a median serum T 1/2 β of 198 h, volume of central compartment of 3.54 L (similar to plasma volume), and clearance of 19.7 mL/h. The median biologic T 1/2 for whole-body retention was 469 h. The highest mean absorbed doses to normal organs (mGy/MBq) were 1.18, 1.11, 0.78, 0.73, and 0.71 for liver, heart wall, lung, kidney, and spleen, respectively. Excellent targeting of metastatic prostate sites in both bone and soft tissue was observed, with an optimal imaging time of 6 days postadministration. The liver and heart were the normal organs that experienced the highest absorbed doses. The pharmacokinetics were similar to other antibodies without major cross-reactivity with normal tissues. A more detailed analysis of lesion targeting in a larger patient population with correlation to immunohistology and standard imaging modalities has been reported.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Biodistribution of a [⁸⁹Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients

et al. 2019

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What influences the activity of Degrader−Antibody conjugates (DACs)

Guo,

Li,

Xie

et al. 2024

European Journal of Medicinal Chemistry

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Antibody therapeutics for treating prostate cancer: where are we now and what comes next?

Vlachostergios

Galletti

Palmer

et al. 2016

Expert Opinion on Biological Therapy

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Progress in the understanding of molecular events of carcinogenesis and cancer evolution as well as the identification of tumor antigens has led to the development of different targeted therapeutic approaches, including the use of monoclonal antibodies (mAbs). Prostate cancer (PC) is highly amenable to mAb targeting given the existence of prostate-specific targets and the natural history and localization of metastatic disease. Areas covered: Several aspects of the PC phenotype, including growth factors, angiogenesis mediators, bone microenvironment signals, and immune evasion pathways, have become areas of ongoing investigation in terms of mAb targeting. These are reviewed. The greatest success so far has been the development of mAbs against prostate-specific tumor antigen (PSMA), which opened an opportunity to improve diagnostic accuracy and simultaneously target metastatic disease. Expert opinion: As mAb use in PC continues to evolve, more accurate imaging of the extent of disease and more effective mAb therapies (naked or conjugated with drugs, toxins or radioactive molecules) are emerging. In addition, the combination of mAbs with other treatment modalities is expected to further improve responses and overall survival. Identification of validated biomarkers is necessary for better recognition of patient subgroups who will derive the greatest benefit from mAb therapy.

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STEAP1 as a predictive biomarker for antibody-drug conjugate (ADC) activity in metastatic castration resistant prostate cancer (mCRPC).

Cited by 4 publications

References 0 publications

Pharmacokinetics and Biodistribution of a [⁸⁹Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients

Pharmacokinetics and Biodistribution of a [⁸⁹Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients

What influences the activity of Degrader−Antibody conjugates (DACs)

Antibody therapeutics for treating prostate cancer: where are we now and what comes next?

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STEAP1 as a predictive biomarker for antibody-drug conjugate (ADC) activity in metastatic castration resistant prostate cancer (mCRPC).

Cited by 4 publications

References 0 publications

Pharmacokinetics and Biodistribution of a [89Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients

Pharmacokinetics and Biodistribution of a [89Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients

What influences the activity of Degrader−Antibody conjugates (DACs)

Antibody therapeutics for treating prostate cancer: where are we now and what comes next?

Contact Info

Product

Resources

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Pharmacokinetics and Biodistribution of a [⁸⁹Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients

Pharmacokinetics and Biodistribution of a [⁸⁹Zr]Zr-DFO-MSTP2109A Anti-STEAP1 Antibody in Metastatic Castration-Resistant Prostate Cancer Patients