Pluvicto (lutetium Lu 177 vipivotide tetraxetan)

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

P1, N=24, Recruiting, The Netherlands Cancer Institute | N=18 --> 24 | Trial completion date: Dec 2023 --> Jul 2025 | Trial primary completion date: Sep 2023 --> Jul 2025

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

P=N/A, N=80, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

P1/2, N=58, Not yet recruiting, University Hospital, Essen

Our results indicate that [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 are neither inhibitors nor substrates of the examined transporters. Therefore, our results show that human ABC and SLC transporters play no central role in the uptake and retention of [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 in the SGs and kidneys nor in the observed toxicities.

The present preclinical and clinical data demonstrate that the combination of EBRT with dose escalation by PSMA-RLT improves tumor control and potentially prolongs survival. This may pave the way for further clinical investigations of this approach to explore the curative potential of the combination therapy.

Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.

P1, N=36, Not yet recruiting, Novartis Pharmaceuticals

P2, N=15, Not yet recruiting, University of Washington | Initiation date: Apr 2024 --> Aug 2024

The therapeutic efficacy of Pluvicto™ at low radioactive doses can be effectively enhanced by the combination with L19-IL2. Our findings warrant further clinical exploration of this novel combination modality.

PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

P1/2, N=30, Not yet recruiting, Rohan Garje

P2, N=62, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Aug 2025 --> Oct 2026 | Trial primary completion date: Apr 2024 --> Jan 2026

P2, N=136, Not yet recruiting, Mayo Clinic | Phase classification: P4 --> P2

P3, N=8000, Not yet recruiting, University College, London

P3, N=450, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

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

P2, N=40, Not yet recruiting, Jonsson Comprehensive Cancer Center

P2, N=60, Recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2026 --> Aug 2025 | Trial primary completion date: May 2026 --> Apr 2024

P2, N=90, Not yet recruiting, Jonsson Comprehensive Cancer Center | Initiation date: Feb 2024 --> Jul 2024

P2, N=60, Recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2028 --> Jan 2027 | Trial primary completion date: Feb 2026 --> Dec 2024

P3, N=469, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2025 --> Sep 2025

P2, N=162, Active, not recruiting, Australian and New Zealand Urogenital and Prostate Cancer Trials Group | Trial completion date: Jun 2024 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Jul 2024

P1, N=60, Recruiting, Endocyte | Trial completion date: Mar 2026 --> Jan 2027 | Trial primary completion date: Mar 2026 --> Jan 2027

P2, N=20, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Twenty-three mCRPC patients of a prospective registry (NCT04833517), who were treated with [Lu]Lu-PSMA-617 RLT and classified as early non-responders were included in this study...Low cGAP (cut-off 0.7) was associated with significant longer survival (17.6 vs. 12.9 months). The novel biomarker cGAP, which represents the temporal change of whole-body TLG normalized by TLP, predicts overall survival in the challenging cohort of patients non-responding to PSMA-RLT.

P3, N=831, Completed, Endocyte | Active, not recruiting --> Completed

P1, N=43, Active, not recruiting, University of California, San Francisco | Phase classification: P1b --> P1 | Trial primary completion date: Apr 2024 --> Jan 2024

P2, N=90, Not yet recruiting, Jonsson Comprehensive Cancer Center

P2, N=60, Recruiting, VA Office of Research and Development | Not yet recruiting --> Recruiting

P2, N=200, Active, not recruiting, Canadian Cancer Trials Group | Recruiting --> Active, not recruiting

P3, N=163, Completed, Mayo Clinic | Enrolling by invitation --> Completed | N=250 --> 163

P1, N=60, Recruiting, Endocyte | Trial completion date: Oct 2025 --> Jan 2026 | Trial primary completion date: Oct 2025 --> Jan 2026

P2, N=32, Not yet recruiting, Maria Sklodowska-Curie National Research Institute of Oncology

P4, N=136, Not yet recruiting, Mayo Clinic

P1/2, N=44, Recruiting, Peter MacCallum Cancer Centre, Australia

P2, N=48, Recruiting, University of California, San Francisco | Not yet recruiting --> Recruiting

P2, N=93, Active, not recruiting, Australian and New Zealand Urogenital and Prostate Cancer Trials Group | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2024 --> Aug 2024

To our knowledge, this is the first large-scale report of real-world US patients treated with 177Lu-PSMA-617. Clinical characteristics and PSA responses observed are consistent with results from the VISION clinical trial demonstrating benefit with 177Lu-PSMA-617 treatment. Subsequent analysis with longer follow up are needed to understand the long-term outcomes associated with 177Lu-PSMA-617 in real-world US patients.

This study provided the unique opportunity to describe real-world outcomes for late stage mCRPC patients treated with PSMA-RLT. The study design did not allow for a direct comparison between the two cohorts. Qualitatively, UKE patients were heavily pre-treated with extensive disease burden at the start of PSMA-RLT.