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ASCO 2024

ASCO 2024: CLARIFY: Positron Emission Tomography Using 64Cu-SAR-bisPSMA in Patients with High-Risk Prostate Cancer Prior to Radical Prostatectomy (A Phase 3 Diagnostic Study)

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL was host to a prostate, testicular, and penile cancers trials in progress poster session. Dr. Michael Gorin presented CLARIFY, a phase III diagnostic study of positron emission tomography (PET) using 64Cu-SAR-bisPSMA in patients with high-risk prostate cancer prior to radical prostatectomy.

Prostate-specific membrane antigen (PSMA) is used as an imaging target for the initial staging of unfavorable intermediate, high risk, or very-high-risk prostate cancer.1 Current PSMA PET agents have high specificity, but low sensitivity for the detection of pelvic lymph node metastases.2,3 The need for improved prostate cancer imaging is reflected in the recurrence rate of up to 20-50% within 10 years of definitive therapy of what was thought to be a disease localized to the prostate gland, with most relapses occurring within five years of definitive therapy.

64Cu-SAR-bisPSMA has two distinct advantages over current PSMA PET agents –bivalent structure and longer half-life (t1/2) of 64Cu (12.7h), compared to monovalent PSMA PET agents utilizing 18F and 68Ga (t1/2<2h).

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In the phase 1 PROPELLER study, 64Cu-SAR-bisPSMA demonstrated 2–3-fold higher tumor uptake and detection of additional prostate cancer lesions, compared to 68Ga-PSMA-11 PET.4

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CLARIFY (NCT06056830) is a multi-center, single-arm, non-randomized, open-label, phase 3 study of 64Cu-SAR-bisPSMA administered to participants with untreated, histopathological confirmed prostate cancer with high-risk features, who are proceeding to radical prostatectomy with pelvic lymph node dissection (PLND; n = 383).

Eligible patients will receive a single administration of 64Cu-SAR-bisPSMA (200 MBg) followed by a PET/CT scan on Day 1 (1-4 hours post-dose) and on Day 2 (24+/-6 hours post-dose). Patients will be assessed for safety and then proceed to the radical prostatectomy with PLND. The specimens from the surgery will be assessed by histopathology to derive the standard of truth (Figure 3).

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The Dav 1 and Day 2 64Cu-SAR-bisPSMA PET/CT scans will be interpreted locally and by three independent blinded central readers. Each reader will assess the scans for the presence of abnormal 64Cu-SAR-bisPSMA uptake. The diagnostic performance of 64Cu-SAR-bisPSMA will be based on the scan result for the respective day independently (Day 1 and 2) matched against the standard of truth.

The primary objective is to assess the diagnostic performance of 64Cu-SAR-bisPSMA PET for the detection of regional nodal metastases – independent primary endpoints for Day 1 and Day 2 PET: Co-primary endpoint of sensitivity and specificity of 64Cu-SAR-bisPSMA PET to detect prostate cancer within the pelvic lymph nodes, compared to the standard of truth. Secondary objectives include the following:

  • To investigate the safety and tolerability of 64Cu-SAR-bisPSMA.
  • To assess the consistency of 64Cu-SAR-bisPSMA PET/CT interpretations for the three central readers.
  • To assess the Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of 64Cu-SAR-bisPSMA PET for pelvic nodal disease
  • To assess the ability of 64Cu-SAR bisPSMA PET to detect prostate cancer (all regions).
  • To assess the ability of 64Cu-SAR bisPSMA PET to detect primary prostate cancer
  • To assess the diagnostic performance of 64Cu-SAR bisPSMA PET to detect regional nodal metastases without subregion matching.

The study is currently open for recruitment in sites in the United States, with additional sites in start-up in Australia.

Presented by: Michael Gorin, MD, Associate Professor, Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, May 31 – Tues, June 4, 2024. 

References:

  1. Schaeffer EM, Srinivas S, Adra N, et al. Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(10): 1067-96.
  2. Hope TA, Eiber M, Armstrong WR, et al. Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial. JAMA Oncol. 2021 Nov 1;7(11):1635-1642.
  3. Pienta KJ, Gorin MA, Rowe SP, et al. A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). J Urol. 2021 Jul;206(1):52-61.
  4. Lengyelova E, Wong V, Lenzo N, et al. 64Cu-SAR-bisPSMA (PROPELLER) positron emission tomography (PET) imaging in patients with confirmed prostate cancer. J Clin Oncol. 2023;41: Suppl 16.