A randomized phase 2 trial of flexible and extended dosing of <sup>177</sup> Lu-PSMA-617 molecular radioligand therapy in mCRPC (FLEX-MRT): Trial in progress update.
Abstract
TPS5121 Background: The U.S. Food and Drug Administration (FDA) approved 177 Lu-PSMA-617 radiopharmaceutical therapy (RPT) for patients with metastatic castration-resistant prostate cancer (mCRPC) with a fixed dosing schedule: Six cycles of 7.4 GBq administered in six-week intervals. However, a patient-tailored more flexible and extended dosing schedule of 177 Lu-PSMA RPT may increase treatment efficacy. In this randomized trial in men with mCRPC, we aim to determine the efficacy of a response-based flexible dosing schedule of 177 Lu-PSMA-617 RPT administered up to 12 treatment cycles compared to the current standard of care. Methods: This is an investigator-initiated prospective phase 2, open-label, randomized, controlled, parallel group, single-center trial. The aim is to assess the 2-year survival rate in mCRPC patients treated with a flexible dosing schedule of 177 Lu-PSMA RPT up to 12 cycles in comparison to the fixed dosing schedule of 6 cycles. Patients with progressive mCRPC post-ARSI, post taxane-based chemotherapy are eligible by PSMA positron emission tomography (PET) VISION trial criteria. Exclusion criteria include prior RPT and less than 6 weeks since the last myelosuppressive therapy. We hypothesized 2-year survival rates of 55% in the investigational group and 30% in the control group. A two-sided log rank test with an overall sample size of 90 subjects (45 treatment group, 45 control group) achieves 80.3% power at a 0.05 significance level to detect a hazard ratio of 0.050. Patients will be randomized in a 1:1 ratio: The investigational arm is treated with up to 12 cycles including potential “treatment holidays” depending on the treatment response (n=45); the control arm receives 6 cycles administered in six-week intervals (n=45). Imaging response to RPT is assessed using 177 Lu-PSMA-617 SPECT/CT after each cycle and PSMA PET/CT during treatment holidays (every 12 weeks), respectively. In the investigational arm, RPT will be re-started after a treatment holiday if the patient experiences a ≥25% PSA progression and an imaging progression according to the Response Evaluation Criteria in PSMA PET/CT (RECIP). Primary endpoint is the 2-year survival rate calculated from the date of the first cycle of RPT. Secondary endpoints include safety by Common Terminology Criteria for Adverse Events (CTCAE) and dosimetry, and determination of overall and progression-free survival (evidence of progression as defined by either radiographic, PSA, or clinical progression, or death from any cause). The FLEX-MRT trial has been approved by the FDA (IND #168362), and the UCLA IRB (#23-000931). The trial is registered on ClinicalTrials.gov (NCT06216249). The FLEX-MRT trial is currently recruiting. Start of enrollment was in August 2024. As of January 27th, 2025, 19 patients have been enrolled. Clinical trial information: NCT06216249 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (19)
Adrien Holzgreve
Astrid Delker
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
Zachary Ells
Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA
Julia Brosch-Lenz
Institute of Nuclear Medicine, Bethesda, MD
Lena Unterrainer
Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany
John Nikitas
University of California, Department of Radiation Oncology, Los Angeles, CA
Shaojun Zhu
Maria Contreras
Ahmanson Translational Theranostics Division, University of California, Los Angeles, Los Angeles, CA
Hamzah Alam
Ahmanson Translational Theranostics Division, University of California, Los Angeles, Los Angeles, CA
Rejah Nabong
Department of Nuclear Medicine and Theranostics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Stephanie Lira
Department of Nuclear Medicine and Theranostics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA
Arseniy Vasilyev
Department of Medicine Statistics Core (DOMStat), Department of Medicine's Division of General Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, CA
Lillian Chen
Department of Medicine Statistics Core (DOMStat), Department of Medicine's Division of General Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, CA
Tristan Grogan
David Elashoff
Catherine Meyer
Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA
Magnus Dahlbom
Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA
Johannes Czernin
Ahmanson Translational Theranostics Division, University of California, Los Angeles, Los Angeles, CA
Jeremie Calais
Luca F. Valle, MD, Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, Radiation Oncology Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA, University of California Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA, Jeremie Calais, MD, PhD, University of California Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA, Department of Nuclear Medicine, University of California Los Angeles, Los Angeles, CA, Amar U. Kishan, MD, Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, University of California Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles, CA