Pluvicto (lutetium Lu 177 vipivotide tetraxetan)

P1/2, N=20, Active, not recruiting, Peter MacCallum Cancer Centre, Australia | Trial completion date: Dec 2023 --> Aug 2025

P2, N=58, Active, not recruiting, Radboud University Medical Center | Recruiting --> Active, not recruiting | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Mar 2025

P3, N=1145, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P2, N=474, Not yet recruiting, Alliance for Clinical Trials in Oncology

P=N/A, N=80, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Initiation date: Sep 2024 --> Dec 2024

P=N/A, N=80, Not yet recruiting, Central Hospital, Nancy, France | Initiation date: Sep 2024 --> Jan 2025

Recent approvals and ongoing investigations of single agents and intensification approaches will keep transforming the mCRPC treatment landscape. Improvement of patient profiling applying recognized genomic, molecular, and clinical predictive and prognostic indicators is fundamental to optimize sequential use of available therapies.

Artificial-intelligence-based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted.

P1, N=6, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P3, N=1126, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting

P2, N=80, Recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2028 --> Apr 2026

P1/2, N=0, Withdrawn, Baptist Health South Florida | N=30 --> 0 | Trial completion date: Jul 2028 --> Oct 2028 | Initiation date: Jul 2024 --> Oct 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Jul 2026 --> Oct 2026

Through whole-body imaging, we identify considerable inter- and intra-patient heterogeneity of mCRPC and potential imaging phenotypes. Regarding uptake and tumour detection, [68Ga]Ga-/[18F]F-PSMA-11/-1007 was superior to [68Ga]Ga-FAPI-46 and 2-[18F]FDG, while the latter two were comparable. Patients who underwent [177Lu]Lu-PSMA-617 RLT based on clinical-decision making had a longer overall survival and could be assigned to the PSMA-dominant phenotype.

P2, N=200, Active, not recruiting, Canadian Cancer Trials Group | Trial primary completion date: Jul 2024 --> Dec 2024

P2, N=15, Recruiting, University of Washington | Not yet recruiting --> Recruiting

P3, N=8000, Recruiting, University College, London | Not yet recruiting --> Recruiting

P2, N=40, Recruiting, Jonsson Comprehensive Cancer Center | Initiation date: Dec 2024 --> Aug 2024 | Not yet recruiting --> Recruiting

P2, N=90, Recruiting, Jonsson Comprehensive Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Dec 2024 --> Aug 2024

P1, N=36, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P2, N=80, Recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2026 --> Nov 2028

P1, N=106, Not yet recruiting, Novartis Pharmaceuticals

P2, N=51, Not yet recruiting, University of Washington

P1, N=24, Not yet recruiting, Blue Earth Therapeutics Ltd

P2, N=40, Not yet recruiting, Jonsson Comprehensive Cancer Center | Initiation date: Jun 2024 --> Dec 2024

P=N/A, N=278, Not yet recruiting, Novartis Pharmaceuticals

P2, N=90, Not yet recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Feb 2028 --> Dec 2028 | Initiation date: Jul 2024 --> Dec 2024 | Trial primary completion date: Feb 2027 --> Dec 2027

P3, N=500, Not yet recruiting, UNICANCER

The PSMA-targeted theranostic 177Lu-PSMA-617 was approved in 2022 for men with PSMA-PET-positive metastatic castration-resistant prostate cancer...PSMA response and resistance to radioligand therapy are mediated by a number of potential mechanisms, and complementary biomarkers beyond PSMA are under development. Understanding the biological determinants of cell surface target regulation and heterogeneity can inform precision medicine approaches to PSMA theranostics as well as other emerging therapies.

P2, N=120, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Dec 2028 --> Oct 2027

P=N/A, N=80, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2029 --> Aug 2029 | Initiation date: May 2024 --> Aug 2024 | Trial primary completion date: May 2028 --> Aug 2028

P4, N=30, Recruiting, Brigham and Women's Hospital | Not yet recruiting --> Recruiting

P=N/A, N=80, Not yet recruiting, Central Hospital, Nancy, France

PARPi's, such as olaparib and rucaparib, have emerged as vital treatments for metastatic CRPC with homologous recombination repair gene mutations, highlighting the importance of personalized medicine...Clinical trials like VISION and TheraP have demonstrated positive outcomes with RLT, particularly [177Lu]PSMA-617, leading to FDA approval...The landscape of PCa treatment is evolving, with significant advancements in both established and novel therapies. The combination of hormonal therapies, chemotherapy, PARPis, immunotherapy, and RLTs, guided by genetic and molecular insights, opens new possibilities for personalized treatment.

Recently, [177Lu]Lu-PSMA-617 has been approved by the U.S. food and drug administration (FDA) for the treatment of prostate cancer patients...In the mouse model with implanted PSMA-positive tumor cells, both [68Ga]Ga-1 and [177Lu]Lu-1 displayed excellent uptake and retention in the tumor. Results indicate that [68Ga]Ga/[177Lu]Lu-1 (68Ga]Ga/[177Lu]Lu-AZ-093) is potentially useful as PSMA-targeting agent for both diagnosis and radiotherapy of prostate cancer.

P1, N=43, Active, not recruiting, University of California, San Francisco | Trial completion date: Apr 2024 --> Apr 2025

P2, N=60, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P1/2, N=30, Recruiting, Vadim S Koshkin | Active, not recruiting --> Recruiting

P1, N=37, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting

177Lu-vipivotide tetraxetan (177Lu-PSMA-617/LuPSMA) received recent EMA approval for metastatic castration-resistant prostate cancer, with promising data for earlier stages...We present a 77-year-old man, with synchronous liver, bone, and lymph node metastatic prostate cancer, having developed a low-risk MDS with SF3B1 mutation, 1 month after the sixth administration of LuPSMA. Although on partial metabolic and biological response with PSA nadir at 7 months after therapy, life quality was significantly altered by MDS.

P2, N=236, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting | N=136 --> 236

P1, N=70, Recruiting, Peter MacCallum Cancer Centre, Australia | N=52 --> 70 | Trial completion date: Dec 2023 --> Jun 2026 | Trial primary completion date: May 2023 --> May 2025

P2, N=80, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting | N=30 --> 80 | Trial primary completion date: Apr 2026 --> Dec 2023