lutetium zadavotide guraxetan (PNT2002) / Lantheus, Eli Lilly - LARVOL DELTA

177 Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer; Primary Endpoint Analysis of the Phase II LUNAR Randomized Trial (ASTRO 2025) - "Materials/ We randomized patients with recurrent omHSPC, characterized by 1-5 lesions outside the prostate or prostate bed on PSMA PET/CT in a 1:1 fashion to receive either SBRT to all metastatic lesions vs. 2 cycles of neoadjuvant 177Lu-PSMA PNT2002 (6.8 GBq/cycles) 6-8 weeks apart followed by SBRT to all metastatic lesions... The addition of 177Lu-PSMA to SBRT more than doubled PFS in this cohort of men with omHSPC, meeting the primary endpoint of the trial, without significantly increasing toxicity."

Clinical • IO biomarker • P2 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • TGFB1

Efficacy of 177Lu-PNT2002 in PSMA-positive mCRPC following progression on an androgen-receptor pathway inhibitor (ARPI) (SPLASH) (ESMO 2024) - P3 | "177Lu-PNT2002 was well tolerated and improved rPFS, ORR, PSA50 and HRQoL in patients with PSMA-positive mCRPC in the pre-chemotherapy setting compared to alternative ARPI."

Clinical • Late-breaking abstract • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

A Phase II Trial In Progress: Alpha-emitting radioNucliDe or Beta-Emitting RadiOnuclide Combined With MEtastasis-Directed Stereotactic Body Radiotherapy for Oligorecurrent Prostate Adenocarcinoma (ANDROMEDA) (ASTRO 2026) - P2 | "Purpose/Objective(s): TBD Background: The recent LUNAR study (NCT05496959) found that adding beta-emitting 177Lutetium-PSMA-targeted radioligand therapy (177Lu-PSMA) to stereotactic body radiation therapy (SBRT) more than doubled median progression-free survival (PFS) compared to SBRT alone in oligorecurrent hormone-sensitive prostate cancer (orHSPC), hazard ratio (HR)=0.37... TBD"

P2 data • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer

Mature phase 1 follow up of alpha emitter 225Ac-J591 with 177Lu-PSMA-I&T in advanced prostate cancer. (ASCO-GU 2025) - P1/2 | "Here, we present mature follow up of a phase 1 dose-escalation trial of 225Ac-J591 plus 177Lu-PSMA-I&T (aka PNT2002)...Previous therapies: 11 (61%) with >1 ARPI, 12 (67%) chemo, 5 (28%) sip-T, 3 (17%) radium-223... The combination of PSMA-targeted alpha (via antibody) plus beta (via small molecule) was feasible. High grade AEs were rare and no new safety signals emerged with longer term follow up. Nearly all patients had PSA decline, and 5 had durable disease control off therapy."

Metastases • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

177-Lutetium-PSMA Before Stereotactic Body Radiotherapy for the Treatment of Oligorecurrent Prostate Cancer, The LUNAR Study (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Prospective randomized phase II trial of 177Lutetium-PSMA therapy neoadjuvant to stereotactic ablative radiotherapy for recurrent oligo-metastatic hormone-sensitive prostate cancer (LUNAR NCT05496959) (ESMO 2025) - P2 | "The only grade 3 adverse events were lymphopenia: 2 patients [4.8%] in the SBRT group and 3 patients [6.7%] in the 177 Lu+SBRT group. Conclusions In this randomized trial, administering 2 cycles of 177Lu-PSMA prior to SBRT improved PFS in men with omHSPC, without increasing toxicity."

Clinical • Late-breaking abstract • Metastases • P2 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

LUNAR: a randomized phase 2 study of Lutetium-PSMA neoadjuvant to ablative radiotherapy for oligorecurrent prostate cancer (clinical trial protocol). (PubMed, BJU Int) - "The addition of Lu-PNT2002 to metastasis-directed therapy alone may potentially further forestall disease progression. The results of this phase 2 trial will determine, for the first time in a randomized fashion, the added benefit of Lu-PNT2002 to SBRT in patients with oligorecurrent mHSPC."

Journal • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ARREST: External Beam and Radioligand Radiotherapy for mCRPC (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Centre hospitalier de l'Universit de Montral (CHUM) | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Alpha-emitting radionuclide or beta-emitting radionuclide combined with metastasis-directed stereotactic body radiotherapy for oligorecurrent prostate adenocarcinoma (ANDROMEDA): A phase II trial. (ASCO 2026) - P2 | "Clinical Trial Registration Number: NCT07150715 Background: The recent LUNAR study (NCT05496959) found that adding beta-emitting 177Lutetium-PNT2002 (177Lu-PSMA) to stereotactic body radiation therapy (SBRT) more than doubled median progression-free survival (PFS) compared to SBRT alone in oligorecurrent hormone-sensitive prostate cancer (orHSPC), hazard ratio (HR)=0.37. However, the relative efficacy compared to novel alpha-emitting 225Actinium-PSMA-617 (225Ac-PSMA) is unknown...Early stopping guidelines include monitoring site-specific grade 4-5 toxicity with a safety threshold of 20% from the time of the first enrolled patient, which would trigger halting the trial and safety consultation. ANDROMEDA is currently open for enrollment."

P2 data • Hormone Sensitive Prostate Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer

Crossover does not confound, it informs: 177lutetium-PSMA-617 as an example. (PubMed, Nat Rev Clin Oncol) - No abstract available

Journal

RECIP: Prognostic Value of 177Lutetium-PSMA Single Photon Emission Tomography and Timing of Response (clinicaltrials.gov) - P=N/A | N=280 | Not yet recruiting | Sponsor: Central Hospital, Nancy, France

New trial • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

RENALUT: Radiopharmaceutical Treatment of Advanced Kidney Cancer (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Not yet recruiting ➔ Recruiting

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

177Lutetium-PSMA-I&T therapy for metastatic castration-resistant prostate cancer (mCRPC): the first multicenter real-world study of 177Lu-PSMA-I&T in Brazil. (PubMed, EJNMMI Rep) - "Our results showed that 177Lu-PSMA-I&T achieved a PSA response comparable to those treated with 177Lu-PSMA-617 in randomized trials, despite our heavily treated patients' characteristics. A significant number of patients had visceral disease with expected lower PSA response, highlighting the need for more active combinations in this subgroup."

Journal • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

STARLiT: STereotActic Body Radiotherapy and 177Lutetium PSMA in Locally Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=45 | Recruiting | Sponsor: Angela Y. Jia, MD PhD | Trial primary completion date: Mar 2026 ➔ Sep 2026

Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

ARREST: External Beam and Radioligand Radiotherapy for mCRPC (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) | Initiation date: Jan 2026 ➔ May 2026

Trial initiation date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Prostate cancer lineage states detected by circulating tumor cell RNA sequencing are prognostic biomarkers for overall survival and resistance to androgen receptor pathway inhibitors and177Lutetium-PSMA-617 (AACR 2025) - "Background: The development of treatment resistance remains universal for metastatic prostate cancer patients, driven by AR alterations and lineage state transitions. We report the largest CTC RNA-seq cohort of patients with metastatic prostate cancer and demonstrate that high-purity CTC RNA-seq identifies prostate cancer lineage states mirroring those in tissue, including an NE phenotype concordant with small cell/neuroendocrine histology. We also identified a more common LumB phenotype defined by persistent AR signaling and high proliferation and associated with poor prognosis and poor response to 177Lu-PSMA-617."

Biomarker • Circulating tumor cells • Clinical • Tumor cell • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

EORTC-2361-GUCG: Radiopharmaceutical treatment of advanced kidney cancer (clinicaltrialsregister.eu) - P1/2 | N=58 | Recruiting | Sponsor: Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi | Not yet recruiting ➔ Recruiting

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

SPECTRA study: A phase II trial of supraphysiological androgen to enhance treatment activity with DNA-damaging agents in men with metastatic castration resistant prostate cancer (mCPRC). (ASCO-GU 2026) - P2 | "To develop more active BAT regimens, we are conducting a trial testing the hypothesis that BAT combined with other DNA-damaging agents including cytotoxic chemotherapy or 177Lutetium-PSMA-617 (LuPSMA) will be more effective than historically observed with BAT alone. This open-label, single center phase II trial is investigating the effects of BAT plus carboplatin AUC 5 IV (Cohort 1), etoposide 100 mg PO daily (Cohort 2), or LuPSMA 7.4 GBq IV (Cohort 3)...Correlative work will assess differences in outcomes based on HRR mutation status and evaluate other genomic and transcriptomic features associated with treatment response/resistance. Cohorts 1 and 2 are open to accrual with 23/63 patients enrolled as of October 2025 (NCT06039371)."

Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HRD

VALOR: Vorinostat and 177Lu-PSMA-617 for the Treatment of PSMA-Low Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial primary completion date: Jul 2026 ➔ Dec 2026

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

VALOR: Vorinostat and 177Lu-PSMA-617 for the Treatment of PSMA-Low Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial primary completion date: Dec 2025 ➔ Jul 2026

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

177Lu-PSMA (177Lu-PNT2002) in PSMA-Positive Adenoid Cystic Carcinoma (clinicaltrials.gov) - P2 | N=1 | Terminated | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=10 ➔ 1 | Trial completion date: Feb 2035 ➔ Jan 2026 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2030 ➔ Nov 2025; Sponsor is no longer producing the study drug, so it was not possible to complete the study.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Adenoid Cystic Carcinoma • Oncology

The role of multimodality imaging in selection, response assessment, and follow-up of patients receiving 177Lutetium-PSMA-therapy. (PubMed, Insights Imaging) - "This review examines the current evidence on imaging biomarkers and complementary diagnostic techniques used for patient selection, treatment monitoring, and response assessment in [¹⁷⁷Lu]Lu-PSMA-617 therapy for metastatic castrate resistant prostate cancer. Interim and longitudinal PSMA-PET/CT offer sensitive detection of progression, quantitative biomarkers for response assessment, and standardised frameworks. Advances in AI, radiomics, and standardisation frameworks may refine prognostication, enable personalised dosimetry, and integrate imaging biomarkers into clinical practice, though further validation is required."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

PSMA-PRED: Intrinsic Validity of Molecular Marker(s) Detection on Tissular Tumoral DNA to Predict the Efficacy of 177Lutetium-PSMA-617 (Lu-PSMA) Treatment for Castration-resistant Metastatic Prostate Cancer (clinicaltrials.gov) - P=N/A | N=120 | Recruiting | Sponsor: Centre Jean Perrin | Trial completion date: Dec 2028 ➔ Jun 2034 | Trial primary completion date: Dec 2026 ➔ Jun 2034

Biomarker • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

STARLiT: STereotActic Body Radiotherapy and 177Lutetium PSMA in Locally Advanced Prostate Cancer (clinicaltrials.gov) - P1/2 | N=45 | Recruiting | Sponsor: Angela Y. Jia, MD PhD | Trial completion date: Sep 2026 ➔ Mar 2027 | Trial primary completion date: Sep 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study. (PubMed, J Clin Oncol) - P2 | "Compared with SBRT alone, the addition of 177Lu-PNT2002 to SBRT significantly improved PFS in patients with orHSPC without an attendant increase in toxicity."

Journal • P2 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor