Clinical Trial Protocol for LPS-Boost: Intensified [¹⁷⁷Lu]Lu-PSMA-617 Treatment for Patients with Metastatic Castration-Resistant Prostate Cancer with Low PSMA-Expressing Disease.

Authors

Amir Iravani, Roman Gulati, Robert Miyaoka, Angela Castellanos Reiger, Delphine L Chen, Meena Kumar, Mark Erickson, Katie Nega, Catherine Meyer, Stephanie Lira, Youngho Seo, Robert R Flavell, Collin C Pritchard, Michael C Haffner, Rosa Nadal Rios, Rajitha Sunkara, Hiba M Khan, Todd Yezefski, Ruben Raychaudhuri, Andrew C Hsieh, Petros Grivas, Heather H Cheng, Evan Y Yu, Michael T Schweizer, Peter S Nelson, Johannes Czernin, Thomas A Hope, Jeremie Calais

Published in

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. Aug 13, 2026. Epub Aug 13, 2026.

Abstract

[¹⁷⁷Lu]Lu-PSMA-617 is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC); however, response rates vary significantly, particularly among patients with low prostate-specific membrane antigen (PSMA) expression on PSMA PET. This multicenter, open-label phase 2 trial evaluates the efficacy and safety of an intensified Lu-PSMA treatment schedule in patients with mCRPC and a whole-body tumor SUV_mean of less than 10 on [⁶⁸Ga]Ga-PSMA-11 PET, a subgroup associated with poorer outcomes with the conventional treatment schedule. Methods: Eligible participants (n = 45) with mCRPC, prior exposure to androgen receptor pathway inhibitor therapy, and progressive disease (defined by the Prostate Cancer Working Group 3 criteria) must have PSMA-positive lesions without PSMA-negative sites and a whole-body tumor SUV_mean of less than 10 on [⁶⁸Ga]Ga-PSMA-11 PET within 3 mo of enrollment. Participants will receive up to 6 cycles of [¹⁷⁷Lu]Lu-PSMA-617 (7.4 GBq per cycle; cumulative dose, 44 GBq) administered at an intensified cadence (days 1 and 8, days 50 and 57), followed by 2 standard cycles every 6 wk. The primary endpoint is prostate-specific antigen (PSA) progression-free survival, with safety as a key secondary endpoint, assessed in accordance with the Common Terminology Criteria for Adverse Events version 5.0. A continuous safety monitoring rule allows early termination if grade 3 or higher adverse hematologic events (excluding lymphopenia) exceed predefined thresholds established by historical data. Additional secondary endpoints include PSA response, radiographic progression-free survival, overall survival, and patient-reported outcomes (Functional Assessment of Cancer Therapy-Prostate, Brief Pain Inventory-Short Form). Exploratory analyses include radiation dosimetry and plasma biomarker assessments. Participants achieving a marked response (≥90% PSA decline to <1 ng/mL or no PSMA-avid disease above liver uptake on 24-h posttreatment SPECT/CT) after the intensified schedule may pause treatment and resume in the event of PSA or clinical progression. Conclusion: By modulating treatment intensity using baseline PSMA expression, this trial aims to improve outcomes in patients predicted to have lower response rates under the standard schedule while maintaining acceptable toxicity.

PMID:
42595485
Bibliographic data and abstract were imported from PubMed on 14 Aug 2026.

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