Delving into the Latest Updates on Lutetium-177-PSMA-I&T with Synapse

Overview

Basic Info

Drug Type

Peptide Conjugate Radionuclide, Therapeutic radiopharmaceuticals

Synonyms-

Target

PSMA

Mechanism

PSMA inhibitors(Prostate-specific membrane antigen inhibitors)

Therapeutic Areas

NeoplasmsMouth and Tooth DiseasesUrogenital Diseases

Active Indication

Prostatic CancerAdenoid Cystic CarcinomaSalivary duct carcinoma+ [1]

Inactive Indication-

Originator Organization

Radboud University Nijmegen

Active Organization

Radboud University Medical Center

Radboud University NijmegenIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori SRL

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

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Abstract Aim The integration of innovative radio-pharmaceutical agents targeting prostate-specific membrane antigen (PSMA) within nuclear medicine has transformed prostate cancer detection and management. This study aims to investigate the present landscape of [177Lu]Lu-PSMA in prostate cancer, elucidating trends, global contributions, scholarly outlets, institutions, and thematic concentrations with an aim to inform forthcoming research endeavors. Methods We systematically probed the Scopus repository for relevant [177Lu]Lu-PSMA literature. An assessment of bibliometric and altmetric data was carried out. Finally, we assessed the correlation between the altmetric attention scores and the number of citations for the retrieved data. Results Spanning January 2015 to July 2023, the study encompassed 466 articles concerning [177Lu]Lu-PSMA therapy for prostate cancer. Predominant citation accolades gravitated towards metastatic castration-resistant prostate cancer investigations and assessments of [177Lu]Lu-PSMA therapy’s safety and efficacy. Further research encompassed adverse effects linked to [177Lu]Lu-PSMA intervention, including xerostomia, thrombocytopenia, anemia, and fatigue. Germany emerged as the primary academic contributor, with The Journal of Nuclear Medicine dominating publications (n = 55). A moderate significant correlation was detected between the number of citations and altmetric attention scores . Conclusion The findings highlight the growing interest and advancements in the utilization of [177Lu]Lu-PSMA therapy in prostate cancer and offer a comprehensive global perspective on future research directions.

01 Jan 2024·Theranostics

Lutetium-177-PSMA therapy for recurrent/metastatic salivary gland cancer: a prospective pilot study

Article

Author: Driessen, Chantal M.L. ; Konijnenberg, Mark W ; Gotthardt, Martin ; Privé, Bastiaan M ; van Herpen, Carla M.L. ; van Ruitenbeek, Niels J. ; van Herpen, Carla M L ; Peters, Steffie M.B. ; Nagarajah, James ; van Engen-van Grunsven, Adriana C H ; Uijen, Maike J M ; Privé, Bastiaan M. ; van Ruitenbeek, Niels J ; Peters, Steffie M B ; van Engen-van Grunsven, Adriana C.H. ; Konijnenberg, Mark W. ; Uijen, Maike J.M. ; Driessen, Chantal M L

There is an urgent need for novel systemic therapies for recurrent/systemic salivary gland cancer, as current treatment options are scarce. [⁶⁸Ga]Ga-PSMA-11 PET/CT revealed relevant uptake of prostate-specific membrane antigen (PSMA) in adenoid cystic carcinoma (AdCC) and salivary duct carcinoma (SDC). Therefore, we assessed the safety, feasibility, efficacy and radiation dosimetry of [¹⁷⁷Lu]Lu-PSMA-I&T treatment in AdCC and SDC patients in a prospective pilot study. Methods: This single-center, single-arm study intended to include 10 recurrent/metastatic AdCC patients and five recurrent/metastatic SDC patients. AdCC patients could only participate in case of progressive and/or symptomatic disease. Patients required ≥ 1 lesion ≥ 1.5 cm with an SUV_max on [⁶⁸Ga]Ga-PSMA-11 PET/CT above liver SUV_mean. Patients were planned to receive four cycles ~ 7.4 GBq [¹⁷⁷Lu]Lu-PSMA-I&T. In case of progressive disease per RECIST 1.1 at mid-treatment evaluation after two cycles, treatment was discontinued. Safety was the primary endpoint. Secondary endpoints included objective response rate (ORR), tumor- and organ-absorbed radiation doses and progression-free survival. Results: After screening, 10 out of 15 (67%) AdCC and two out of 10 (20%) SDC patients were eligible. Two patients (17%) demonstrated grade 3 treatment-related toxicity: lymphocytopenia (8%) and hyponatremia (8%). No dose-limiting toxicities occurred. In the AdCC cohort, six patients (60%) completed the four treatment cycles. Due to progressive disease, treatment was discontinued after two cycles in three patients (30%) and after one cycle in one patient (10%). No objective responses were observed (ORR: 0%). Three AdCC patients (30%) showed stable disease ≥ 6 months (7, 17 and 23 months). None of the two SDC patients completed the treatment: one patient deteriorated after the first cycle, while the other had progressive disease after two cycles. The high screen failure rate due to insufficient PSMA uptake resulted in premature closure of the SDC cohort. Dosimetry revealed low tumor-absorbed doses (median 0.07 Gy/GBq, range 0.001-0.63 Gy/GBq). Conclusions: [¹⁷⁷Lu]Lu-PSMA-I&T in AdCC and SDC patients was safe and generally well-tolerated. However, efficacy was limited, likely due to low tumor-absorbed doses. For SDC, [¹⁷⁷Lu]Lu-PSMA-I&T appears unfeasible due to insufficient PSMA uptake.

01 Jul 2023·European Urology Open Science

AR and PI3K Genomic Profiling of Cell-free DNA Can Identify Poor Responders to Lutetium-177-PSMA Among Patients with Metastatic Castration-resistant Prostate Cancer

Article

Author: Üstmert, Sezgin ; Maes, Alex ; Lesage, Karl ; Van Bos, Eva ; Lavent, Filip ; Vanwelkenhuyzen, Jan ; Lindberg, Johan ; Beels, Laurence ; Ost, Piet ; Grönberg, Henrik ; De Laere, Bram ; Van Bruwaene, Siska

Lutetium-177 prostate-specific membrane antigen radioligands (¹⁷⁷Lu-PSMA) are new therapeutic agents for the treatment of metastatic castration-resistant prostate cancer (mCRPC). We evaluated the prognostic value of circulating tumour DNA (ctDNA) profiling in patients with mCRPC starting treatment with ¹⁷⁷Lu-PSMA I&T. Between January 2020 and October 2022, patients with late-stage mCRPC (n = 57) were enrolled in a single-centre observational cohort study. Genomic alterations in the AR gene, PI3K signalling pathway, TP53, and TMPRSS2-ERG were associated with progression-free survival (PFS) on Kaplan-Meier and multivariable Cox regression analyses. Median PFS of 3.84 mo (95% confidence interval [CI] 3.3-5.4) was observed, and 21/56 (37.5%) evaluable patients experienced a prostate-specific antigen response of ≥50% during treatment. Among 46 patients who provided a blood sample for profiling before ¹⁷⁷Lu-PSMA treatment. ctDNA was detected in 39 (84.8%); higher ctDNA was correlated with shorter PFS. Genomic structural rearrangements in the AR gene (hazard ratio [HR] 9.74, 95% confidence interval [CI] 2.4-39.5; p = 0.001) and alterations in the PI3K signalling pathway (HR 3.58, 95% CI 1.41-9.08; p = 0.007) were independently associated with poor ¹⁷⁷Lu-PSMA prognosis on multivariable Cox regression. Prospective evaluation of these associations in biomarker-driven trials is warranted.Patient summaryWe examined cell-free DNA in blood samples from patients with advanced metastatic prostate cancer who started treatment with lutetium-177-PSMA, a new radioligand therapy. We found that patients with genetic alterations in the androgen receptor gene or PI3K pathway genes did not experience a lasting benefit from lutetium-177-PSMA.

100 Deals associated with Lutetium-177-PSMA-I&T

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Phase 2	-	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori SRL	07 Jun 2023
Salivary duct carcinoma	Phase 2	NL	Radboud University Medical Center	26 May 2020
Adenoid Cystic Carcinoma	Phase 2	-	Radboud University Nijmegen	-
Salivary Gland Neoplasms	Phase 2	-	Radboud University Nijmegen	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2023	Not Applicable	Metastatic castration-resistant prostate cancer	51	lutetium-177-PSMA-617 (Lu-177) (Hgb ≤10 g/dL or received RBC Tx)	oacjnmknjz(ytvdmwseuk) = bnhcsycbcm atbmzixnpx (dubkmbqznr, 4.43 - NA)	-	31 May 2023