Pluvicto (lutetium Lu 177 vipivotide tetraxetan) / Novartis, Otsuka - LARVOL DELTA

PSMAddition: An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC (clinicaltrials.gov) - P3 | N=1145 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Jul 2025 ➔ Jan 2025

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

In Vitro and In Vivo Study of Novel PSMA-Targeted Radioligands: Enhancing Tumor Uptake and Therapeutic Efficacy through Zwitterionization and Albumin-Binding Strategies. (PubMed, Mol Pharm) - "The TRT results showed that a single injection of 7.4 MBq of [177Lu]Lu-BWD significantly inhibited the growth of PC3-PIP tumors, and it was superior to that of [177Lu]Lu-PSMA-617 under the same conditions. [177Lu]Lu-BWD with greatly enhanced tumor uptake and retention demonstrated remarkable therapeutic efficacy using significantly lower dosages for clinical translation to treat PCa with high level of PSMA expression."

Journal • Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

177Lutetium-PSMA Therapy in a Patient With Concurrent Prostate Cancer and Renal Cell Carcinoma. (PubMed, Clin Nucl Med) - "Despite the beneficial effects of 177Lu-PSMA therapy in metastatic prostate cancer, its efficacy in nonprostatic malignancies is under investigation. In this case, 177Lu-PSMA-617 did not show remarkable therapeutic efficiency in RCC."

Journal • Genito-urinary Cancer • Musculoskeletal Pain • Oncology • Pain • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

Targeted Radionuclide Therapy in Diffuse Intrinsic Brainstem Gliomas: Exploring Options Beyond the Finish Line. (PubMed, Clin Nucl Med) - "We present a 12-year-old girl diagnosed with DIPG in July 2022, who received 60 Gy, 30 fractions of radical radiotherapy over 6 weeks, followed by temozolomide. With residual disease, the patient was referred to our department for the possibility of radiotheranostics. She underwent 68Ga PSMA PET/CT, which revealed tracer accumulation in the pontine mass and was subsequently given 2 cycles of Lu-177 PSMA 617 and 1 cycle of Ac-225 PSMA 617 therapy."

Journal • Brain Cancer • Glioma • Oncology • Pediatrics • Solid Tumor

UPLIFT: Abemaciclib Before 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Vadim S Koshkin | Trial completion date: Jul 2027 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ May 2026

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

A scalable protocol for the radiosynthesis of clinical grade lutetium-177-labeled theranostic agents. (PubMed, Nat Protoc) - "177Lu is typically incorporated into theranostics using the chelators 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) and 2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)pentanedioic acid (DOTAGA) that are used to prepare the 177Lu-radiopharmaceutical [177Lu]Lu-DOTA-TATE, [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T. With robust procedures that accommodate 177Lu activity levels from 5 to 100 GBq, the procedures ensure stability for up to 8 h postproduction and achieve an average activity yield of 98%. As proven in over 1,000 patient cycles, this methodology is adaptable to both centralized production facilities and regional centers, enabling versatile application across small and large-scale production settings."

Journal • Review

Radioimmunotherapy-associated myeloid neoplasms: Real-world multicenter retrospective study using TriNetX database. (ASCO 2025) - "This study aims to investigate the risk of t-MNs following treatment with Lutathera (177Lu-DOTATATE) and Pluvicto (177Lu-PSMA-617) in patients with neuroendocrine tumors and metastatic castration-resistant prostate cancer. This is the largest study reporting the incidence of t-MN associated with RIT. Our study demonstrated a significant risk of therapy-related t-MNs following RIT, even in patients who did not receive additional chemoradiotherapy. Given the short follow-up, we hypothesize that the risk may increase with longer-term follow-up."

IO biomarker • Real-world • Real-world evidence • Retrospective data • Acute Myelogenous Leukemia • Castration-Resistant Prostate Cancer • Endocrine Cancer • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Neuroendocrine Tumor • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor

Recurrent pulmonary lymphangitis carcinomatosis detected on 177Lu-PSMA-617 post-therapy scan in mCRPC with negative PSMA PET and HRCT. (PubMed, Eur J Nucl Med Mol Imaging) - No abstract available

Journal • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Combination prostate-specific membrane antigen-targeted radiopharmaceutical therapy in metastatic prostate cancer. (PubMed, Q J Nucl Med Mol Imaging) - "The regulatory approvals for 177Lu-PSMA-617 radiopharmaceutical therapy in both the pre- and post-chemotherapy metastatic castration resistant prostate cancer clinical space have paved the way for the implementation of this life-prolonging therapy in clinical practice...Biologically rational combination therapies across various phases of prostate cancer will lead to more optimal patient outcomes than what can be achieved with monotherapy. This article summarizes select clinical trials on prostate-specific membrane antigen-targeted radiopharmaceutical therapy in combination with other treatments that are either actively accruing or have provided preliminary results."

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

PSMA targeted Therapy: From molecular mechanisms to clinical breakthroughs in castration-resistant prostate cancer. (PubMed, Eur J Med Chem) - "We critically examine the latest advancements in PSMA-targeted treatment strategies, including radioligand therapy (e.g., 177Lu-PSMA-617), antibody-drug conjugates, bispecific T-cell engagers, and small-molecule PSMA inhibitors...Ongoing clinical trials are actively exploring combinatory approaches, integrating PSMA-targeted therapy with radiotherapy, chemotherapy, and immunotherapy to optimize therapeutic efficacy. This review underscores the promise of PSMA-targeted strategies in advancing precision medicine for mCRPC, paving the way for improved survival outcomes and a better quality of life for affected patients."

IO biomarker • Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

The STAMPEDE2 trial: A site survey of current patterns of care, access to imaging, and treatment of metastatic prostrate cancer in Nigeria. (ASCO 2025) - "Prostate cancer treatment modalities are available; however, access to novel agents such as abiraterone and enzalutamide was reported in 73% of centres...Clinicians expressed strong interest in participating in trials, though some gaps in infrastructure, particularly in rural areas, and limited access to advanced treatments like 177Lu-PSMA-617 were noted. The findings underscore Nigeria's potential readiness for the STAMPEDE2 trial, as well as other clinical trials and collaborative research, bolstered by an expanding radiotherapy infrastructure and clinician enthusiasm for advanced therapeutic approaches. Initiatives like the Cancer Health Fund (CHF) and the National Cancer Access Partnership (NCAP) represent significant steps towards equitable cancer care."

Metastases • Oncology • Prostate Cancer

Barriers and challenges for precision medicine and evidence-based oncology in genitourinary tumors in Latin America: insights from the LACOG 1024 survey CIELO. (ASCO 2025) - "Regarding access to therapies, 48.1% of the participants had access to adjuvant pembrolizumab for renal cell carcinoma, 42.7% to olaparib monotherapy for PC, 41.2% to enzalutamide for non-metastatic castration-sensitive PC, 38.2% to adjuvant nivolumab for urothelial carcinoma, and 31.3% to pembrolizumab for non-muscle invasive bladder cancer. Conversely, treatments such as first-line enfortumab vedotin with pembrolizumab (18.3%), erdafitinib (18.3%), Lu 177 vipivotide tetraxetan (9.9%), relugolix (6.9%), and belzutifan (1.5%) faced significant access barriers... To the best of our knowledge, this is the largest survey conducted on this topic to date in LATAM. The results underscore substantial barriers to the adoption of precision medicine, driven predominantly by limited insurance coverage and financial constraints. Enhancing access to advanced diagnostics and therapies is crucial for bringing regional practices in line with global standards and for improving patient..."

Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

Real-world outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) receiving guideline-recommended therapies after treatment with 177Lu-PSMA-617: A real-world prostate cancer disease observation (PRECISION) data platform analysis. (ASCO 2025) - "Guideline-recommended therapies included abiraterone, enzalutamide, darolutamide, apalutamide, cabazitaxel, docetaxel, pembrolizumab, sipuleucel-T, niraparib, olaparib, talazoparib, rucaparib, and radium-223. In this real-world analysis, the majority of patients who received guideline-recommended therapies after 177Lu-PSMA-617 achieved at least a PSA50 response, suggesting that 177Lu-PSMA-617 treatment does not preclude response to other subsequent therapies."

Clinical • Metastases • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urology

Real-world comparison of lutetium-177 vipivotide tetraxetan in advanced castration resistant metastatic prostate cancer patients in Appalachia. (ASCO 2025) - "WVU results call to action the need for improving patient selection or applying different selection criteria for using Lu-177. Other considerations include the using Lu-177 earlier in prostate cancer treatment, targeted radiation, and using novel isotopes or new PSMA linker molecules. Summary of Lu-177 trials and WVU data."

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

Artificial intelligence to predict outcome after [177Lu]Lu-PSMA for metastatic castration-resistant prostate cancer: Preliminary results from a multicentric prospective study. (ASCO 2025) - "Funded by No funding sources reported Clinical Trial Registration Number: CEMEN 202406 Background: [177Lu]Lu-PSMA-617 was approved for metastatic castration-resistant prostate cancer, but only 46% of patients achieved a PSA response in the phase 3 VISION trial... Preliminary results show that SelectPSMA, an AI-based technology, identified patients with lower likelihood of PSA response and shorter progression-free survival after [177Lu]Lu-PSMA radiopharmaceuticals. Results of multi-centric analysis including mature OS data will be presented at the conference."

Biomarker • Clinical • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

177Lu-vipivotide tetraxetan PSMA vs cabazitaxel in metastatic castration-resistant prostate cancer: A real-world analysis using the TriNetX database. (ASCO 2025) - "Patients were stratified into four groups: Group 1A (Docetaxel → Abiraterone/androgen receptor inhibitor [ARI] → 177Lu-PSMA), Group 1B (Docetaxel → Abiraterone/ARI → Cabazitaxel), Group 2A (Abiraterone/ARI → Docetaxel → 177Lu-PSMA), and Group 2B (Abiraterone/ARI → Docetaxel → Cabazitaxel). Our real-world analysis demonstrates that 177Lu-PSMA significantly improves survival and has a more favorable safety profile compared to Cabazitaxel in mCRPC. These findings support its role as a preferred third-line option. However, further large-scale studies are needed to validate these findings in broader patient populations Incidence of side effects in patients who received 177Lu-PSMA vs cabazitaxel as a third line agent for mCRPC."

Clinical • Metastases • Real-world • Real-world evidence • Anemia • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Xerostomia

Clinical outcomes of prompt versus deferred 177Lu-PSMA-617 initiation for metastatic castration-resistant prostate cancer (mCRPC) based on prior androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy exposure: A real-world prostate cancer disease observation (PRECISION) data platform analysis. (ASCO 2025) - "In this large real-world study, prompt initiation of 177Lu‑PSMA‑617 (after only 1 ARPI and 1 taxane) showed superior clinical outcomes versus deferred initiation of 177Lu‑PSMA‑617. Patients were more likely to achieve a PSA reduction ≥50% and ≥80% and had longer OS with prompt initiation of 177Lu‑PSMA‑617. These results may help to guide treatment sequencing in clinical practice."

Clinical • Clinical data • Metastases • Real-world • Real-world evidence • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Performance of 177Lu-PSMA-I&T for RLT in mCRPC: First prospective data of a multicenter Swiss registry study. (ASCO 2025) - "The first prospective multicenter registry data demonstrated that 177Lu-PSMA-I&T therapy is safe and effective in mCRPC. When comparing our real-world data to previously reported phase III studies, the toxicity profile appears similar to that of 177Lu-PSMA-617, with comparable treatment efficacy."

Clinical • Acute Kidney Injury • Anemia • Castration-Resistant Prostate Cancer • Leukopenia • Nephrology • Neutropenia • Prostate Cancer • Renal Disease • Thrombocytopenia

Lutetium-177-PSMA-617 in oligo-metastatic hormone sensitive prostate cancer (BULLSEYE trial). (ASCO 2025) - P2 | "[177Lu]Lu-PSMA-617 showed promising efficacy as monotherapy in oligometastatic hormone sensitive prostate cancer patients to defer from androgen deprivation therapy, with minimal and mostly transient side effects. Following surgery and external beam radiotherapy, could become a third metastases-directed therapeutic option for oligometastatic prostate cancer patients to prolong ADT-free interval."

Metastases • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • Xerostomia

Predictive and prognostic value of baseline PSMA-PET total tumor volume and SUV mean within ENZA-p, a randomized phase II trial of enzalutamide versus enzalutamide plus [177Lu] Lu-PSMA-617 (ANZUP1901). (ASCO 2025) - P2 | "Participants (pts) with mCRPC not previously treated with chemotherapy or AR antagonist (abiraterone permitted) and [68Ga]Ga-PSMA-avid disease were randomized (1:1) to either enza-alone or enza + LuPSMA using adaptive-dosed [177]Lu LuPSMA-617 7.5 GBq for (2 or 4 doses). Baseline PSMA-TTV was prognostic of shorter OS with enza-alone, but not with the addition of LuPSMA-617. In contrast to LuPSMA-617 monotherapy, PSMA SUVmean was neither predictive nor prognostic of improved OS, nor of PSA-PFS when LuPSMA-617 was given together with enza as first line treatment for mCRPC."

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

Comparative effectiveness of cabazitaxel (C) vs. lutetium Lu-177 vipivotide tetraxetan (Lu) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2025) - "Funded by No funding sources reported Background: C and Lu are both life-prolonging therapies for pts with mCRPC after progression on androgen receptor pathway inhibitor (ARPI) and docetaxel (D). This is the largest real-world data to date assessing the comparative effectiveness of Lu vs. C, and it showed significantly longer rwTTNT and rwOS with Lu compared to C in pts with mCRPC pretreated with ARPI and D. Limitations: retrospective nature, selection bias, missingness, lack of randomization, etc. and residual confounding in real-world datasets."

Clinical • HEOR • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Survival and hospitalizations with lutetium (Lu)-177 vipivotide tetraxetan in veterans with underlying genomic alterations. (ASCO 2025) - "In US Veterans treated with 177Lu-PSMA-617, median OS was 11.4 months, shorter than observed in other cohorts, although the mean age was higher. Comorbidities were prognostic for mortality and hospitalization while age was not. Veterans who had TSG alterations had significantly shorter OS in unadjusted and adjusted analyses, suggesting that patients with TSG alterations are less likely to benefit from 177Lu-PSMA-617 and could consider different treatment modalities."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PTEN • RB1 • TP53

Precision diagnostics in prostate cancer treatment (PREDICT): A phase 2 multi-arm biomarker based study (Alliance A032102). (ASCO 2025) - P2 | "Patients with Rb loss (DNA), Rb functional loss signature (RNA), NEPC signature (RNA) will be allocated to treatment with the EZH1/2 inhibitor valemetostat. Patients with at least 2 of 3 tumor suppressor gene DNA alterations (TP53, RB1, PTEN), FANC alteration (DNA), or SLFN11 overexpression (RNA) will be allocated to cabazitaxel plus carboplatin. Patients without any study-defined alterations will be allocated to physician choice treatment with either cabazitaxel, ARPI, or 177Lu-PSMA-617...A Simon two-stage minimax design per arm was used to determine whether the response rate for measurable disease patients was greater than 0.20. This design has a type 1 error equal to 0.05 and has power equal to 0.90 if the probability of response is 0.37."

Biomarker • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • EZH2 • PTEN • RB1 • SLFN11 • TP53

Integrated analysis of tissue genomic sequencing and high purity circulating tumor cell RNA sequencing for prostate cancer lineage states as a prognostic factor for survival and resistance to 177Lu-PSMA-617 in patients with metastatic castrate resistant prostate cancer. (ASCO 2025) - "Lineage states detected by high purity CTC RNAseq are prognostic for poor OS and decreased benefit from 177Lu-PSMA-617. The presence of high-risk genetic mutations including RB1 is prognostic for poor OS and combined evaluation of high-risk genetic mutation status with lineage state phenotype identifies patients with the worst clinical outcomes that would benefit from treatment intensification and early disease monitoring for these more aggressive subtypes of mCRPC."

Biomarker • Circulating tumor cells • Clinical • Metastases • Tumor cell • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • HRD • PTEN • RB1 • TP53

Assessment of PSMA PET/CT derived predictive markers for 177Lu-PSMA-617 treatment outcomes: Results from the U.S. Expanded-Access program. (ASCO 2025) - P=N/A | "Quantitative analysis outperformed visual analysis in predicting the outcome of mCRPC with Lu-PSMA therapy in the EAP cohort. Total tumor SUVmean was identified as the most robust predictor for PSA PFS, while TLQ showed promise as a predictor for OS. Incorporating these predictors into clinical decision-making for pre-Lu-PSMA therapy could aid in patient selection and treatment planning."

Biomarker • Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Salivary Gland Cancer • Solid Tumor