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

177Lu-PSMA-617 with ipilimumab (ipi) and nivolumab (nivo) in metastatic castration-resistant prostate cancer (mCRPC): An investigator-initiated phase 2 trial (EVOLUTION; ANZUP2001). (ASCO 2025) - P2 | "Median age was 70 years [range: 45-83]; 80% had prior docetaxel. LuPSMA+ICI was associated with improved PSA-PFS 12m in mCRPC. The spectrum of AEs were keeping with established toxicities however significantly higher with LuPSMA+ICI, and frequency of ICI-related myocarditis lead to early trial cessation. *Safety population."

Metastases • P2 data • Anemia • Castration-Resistant Prostate Cancer • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hepatology • Immunology • Infectious Disease • Oncology • Pneumonia • Prostate Cancer • Respiratory Diseases • Septic Shock • Solid Tumor • Thrombocytopenia

A randomized phase II study of 177Lu-PSMA-617 vs docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) and PSMA-positive disease: Canadian Cancer Trials Group (CCTG) study PR.21 (ESMO 2025) - P2 | "Table: LBA89 Outcome LU-P (n=100) Median DOC (n=99) Median HR (LU-P/DOC) p-value rPFS(mo) 8.6 (90%CI 7.13 -10.60) 10.7 (90%CI 7.82-11.10) 1.02 (90%CI 0.77-1.35) 0.54 (1 sided) OS(mo) 14.3 (90%CI 10.8-16.6) 18.2 (90%CI 16.1-23.0) 1.64 (90%CI 1.14-2.35) 0.02 (2 sided) Conclusions In the PR21 study population of patients with chemo-naive mCRPC, there was no significant rPFS difference between LU-P and DOC. PSA RR, ORR and frequency of treatment related grade 3/4 AEs favoured LU-P; OS favoured the arm assigned to DOC at randomization."

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

LASER: A Phase 2 Trial of 177Lu-PSMA-617 as Systemic Therapy for RCC. (PubMed, J Nucl Med) - " This prospective trial aims to evaluate the safety and preliminary efficacy of 177Lu-PSMA-617 in patients with advanced PSMA-positive ccRCC. The results of this study may support the clinical development of PSMA-targeted radiopharmaceutical therapy as a novel treatment option for patients whose disease has progressed after standard systemic therapies."

IO biomarker • Journal • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

Health-related quality of life, pain, and symptomatic skeletal events in the phase 3 PSMAddition study of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) combined with ADT and ARPI in patients with PSMA-positive mHSPC. (ASCO-GU 2026) - P3 | "Clinical Trial Registry Number: NCT04720157. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • HEOR • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Prostate Cancer

Prognostic and predictive value of baseline PSMA-PET total tumour volume and SUVmean in metastatic castration-resistant prostate cancer in ENZA-p (ANZUP1901): a substudy from a multicentre, open-label, randomised, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "Baseline PSMA-TTV is prognostic for overall survival and predictive for a beneficial effect on overall survival with the addition of [177Lu]Lu-PSMA-617 to enzalutamide as first-line treatment for high-risk metastatic castration-resistant prostate cancer. By contrast, PSMA SUVmean was not prognostic for PSA progression-free survival or overall survival when [177Lu]Lu-PSMA-617 was administered with enzalutamide."

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

STARLiT: A Single Arm Phase I/II Trial of STereotActic Body Radiotherapy and 177 Lutetium PSMA in Locally Advanced Prostate Cancer (ASTRO 2025) - "The most common treatment for this patient subset is radiation therapy (RT) plus long-term androgen deprivation therapy (ADT) for 18-36 months with consideration for the addition of abiraterone acetate...STARLiT aims to evaluate the safety of combining 177Lu-PSMA-617 with SBRT to the prostate and to determine whether 177Lu-PSMA-617 can replace ADT to improve disease control by use of cytotoxic agents, avoid side effects and improve patient compliance to receive systemic therapy... The trial was activated in February 2025 and aims to complete accrual within 18 months with a 5-year follow-up."

Metastases • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Emerging Therapeutic Strategies in Prostate Cancer: Targeted Approaches Using PARP Inhibition, PSMA-Directed Therapy, and Androgen Receptor Blockade with Olaparib, Lutetium (177Lu)Vipivotide Tetraxetan, and Abiraterone. (PubMed, J Clin Med) - "We conclude that the optimal use of PARP inhibitors, PSMA-targeted RLT, and ARPIs requires a personalized strategy guided by molecular profiling, functional imaging, prior treatment exposure, and safety considerations. This clinically focused overview aims to support evidence-based decision-making in an increasingly complex treatment landscape."

Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • BRCA1 • BRCA2 • HRD

LuPARP: Phase 1 trial of 177Lu-PSMA-617 and olaparib in patients with metastatic castration resistant prostate cancer (mCRPC). (ASCO 2023) - P1 | " 29 pts (median age 70 years: range: 52-84; prior docetaxel: 97%; prior androgen receptor pathway inhibitor: 100%) received 177Lu-PSMA-617 on day 1 with escalating doses of olaparib (cohorts 1-6: 50mg - 300 mg BD days 2-15) or alternate olaparib schedules (cohort 7: 200 BD days - 4 to 14; cohort 8: 300 BD days - 4 to 14; cohort 9: 300 mg BD days -4 to 18) for up to 6 cycles. The combination of 177Lu-PSMA-617 and olaparib is well tolerated and has promising activity. Three further patients are being enrolled to cohort 9 to confirm the RP2D ahead of dose-expansion. Clinical trial information: NCT03874884."

Clinical • Metastases • P1 data • Anemia • Anorexia • Constipation • Dental Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Disorders • Neutropenia • Oncology • Prostate Cancer • Solid Tumor • Thrombocytopenia • Xerostomia • FOLH1

Overall survival in men with metastatic castration-resistant prostate cancer treated with olaparib or lutetium-177-PSMA-617 following prior systemic therapy. (ASCO-GU 2026) - "The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

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

LuPARP: Phase I trial of [177Lu]Lu-PSMA-617 (LuPSMA) and olaparib in patients (pts) with metastatic castration resistant prostate cancer (mCRPC) (ESMO 2025) - P1 | "Results Between Sept 2019 to Nov 2023, 48 pts were enrolled; median age 70 years, all received prior ARPI, 98% received prior docetaxel. Of the 8 pts with RECIST measurable disease in DL9, 7 (88%) had a partial response. Conclusions The combination of LuPSMA with intermittent olaparib dosing is safe and has promising activity."

Clinical • Metastases • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

Clonal hematopoiesis (CH) in participants with metastatic castration-resistant prostate cancer (mCRPC) receiving 177Lu-PSMA-617 or cabazitaxel: An exploratory post-hoc analysis of a randomized phase II trial (TheraP; ANZUP 1603). (ASCO 2025) - P2 | "Here, we explored CH in the TheraP trial randomizing participants (pts) with docetaxel-refractory mCRPC to cabazitaxel or 177Lu-PSMA-617 (NCT03392428). 177Lu-PSMA-617 was associated with a greater number of new CH mutations, especially in DNA damage repair genes, compared to cabazitaxel. Whilst the clinical relevance of this finding in a population of patients with heavily-treated mCRPC is unclear, CH emergence and expansion may have implications as radioligand therapy is used as an earlier line of therapy."

Clinical • Metastases • P2 data • Retrospective data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ASXL1 • CHEK2 • DNMT3A • PPM1D • TET2

Lutetium-177-PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial. (PubMed, Nat Med) - P2 | "We anticipate our ctDNA fraction-aware analytical framework will aid future precision management strategies for [¹⁷⁷Lu]Lu-PSMA-617 and other PSMA-targeted therapeutics. ClinicalTrials.gov identifier: NCT03392428 ."

Circulating tumor DNA • Journal • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ATM • FOLH1 • PTEN

Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition) (ESMO 2025) - P3 | "Conclusions Combining 177 Lu-PSMA-617 with ADT + ARPI significantly improved rPFS in this first phase 3 trial of radioligand therapy in mHSPC. Safety findings were consistent with the known profile and QoL was not adversely affected."

Clinical • Late-breaking abstract • Metastases • P3 data • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Evolution: Phase II study of radionuclide 177Lu-PSMA-617 therapy versus 177Lu-PSMA-617 in combination with ipilimumab and nivolumab for men with metastatic castration-resistant prostate cancer (mCRPC; ANZUP 2001). (ASCO-GU 2023) - P2 | " This open label, multicentre, phase 2 study will randomly assign 100 participants with mCRPC in a 2:1 ratio stratified by site and prior exposure to docetaxel to either: the experimental combination of 177Lu-PSMA-617 7.5 GBq every 6 weeks for up to 6 doses plus ipilimumab 3 mg/kg every 6 weeks x 4 doses and nivolumab 1 mg/kg every 3 weeks x 8 doses during induction, followed by nivolumab 480 mg every 4 weeks x 18 doses during maintenance or 177Lu-PSMA-617 alone. Accrual as of the 11th of October 2022 is 23. Clinical trial information: NCT05150236."

Combination therapy • IO biomarker • Metastases • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Insights from PSMAfore: impact on health-related quality of life. (PubMed, Transl Androl Urol) - No abstract available

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

PSMAcTION trial-in-progress: a phase II/III randomized trial of [225Ac]Ac-PSMA-617 (225Ac-PSMA-617) versus standard of care in patients with PSMA-positive metastatic castration-resistant prostate cancer who progressed on or after [177Lu]Lu-PSMA therapy (ESMO 2025) - P2/3 | "Background Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) [ 177 Lu]Lu-PSMA-617 prolonged radiographic progression-free survival (rPFS) in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in the taxane-naive (PSMAfore) and post-taxane (VISION) settings...In phase 3, ∼420 patients will be randomized to 225 Ac-PSMA-617 for ≤ 6 cycles or investigator's choice of SoC (excluding PARP inhibitors and immunotherapy except sipuleucel-T)...Safety follow-up will occur at 56 and 30 days (+7) after the last dose of 225 Ac-PSMA-617 and SoC, respectively, with long-term follow-up for up to 5 years. As of April 2025, the first patient first visit occurred in the Asia-Pacific region."

Clinical • Metastases • P2/3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A phase Ib study of a single priming dose of 177Lu-PSMA-617 coupled with pembrolizumab in metastatic castration resistant prostate cancer (mCRPC) (ESMO 2022) - P1b | "Thirteen (33%), 8 (19%), and 22 (52%) pts had PD on abiraterone, AR antagonist, or both, respectively. Conclusions 177 Lu-PSMA-617 as a single priming dose followed by pembrolizumab demonstrates a favorable safety profile and encouraging anti-tumor activity, with durable responses observed in mCRPC without genomic selection for microsatellite instability or high mutational burden. Further investigation of the combination is warranted."

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • MSI • TMB

Novartis delivered high single-digit sales growth, achieved 40% core margin and further advanced the pipeline in 2025 (GlobeNewswire) - "Sales growth driven by continued strong performance from priority brands including Kisqali (+57% cc)...Pluvicto (+42% cc), Scemblix (+85% cc)...Kisqali (USD 1 321 million, +44% cc) sales grew strongly across all regions, with strong momentum from the early breast cancer indication as well as continued share gains in metastatic breast cancer...Pluvicto (USD 605 million, +70% cc) sales reflect continued strong demand...Scemblix (USD 391 million, +87% cc) sales grew across all regions...Lutathera (USD 203 million, +5% cc) sales grew mainly in the US, Europe and Japan..."

Sales • Castration-Resistant Prostate Cancer • Chronic Myeloid Leukemia • Gastrointestinal Neuroendocrine Carcinoma • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Pancreatic Neuroendocrine Tumor

Safety data from UPLIFT: Phase I/II study of CDK4/6 inhibition with abemaciclib to upregulate PSMA expression prior to 177Lu-PSMA-617 treatment in patients with metastatic castrate resistant prostate cancer (mCRPC). (ASCO-GU 2026) - P1/2 | "Clinical Trial Registry Number: NCT05113537. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer. (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CHGA • PTEN • RB1 • SSTR2 • SYP • TP53

Latest Clinical Data for Novel mHSPC Therapies (ASCO-GU 2026) - "a. Recent updates for current and ongoing trials with PARP inhibitors, AKT inhibitors, and PSMA-targeted radioligand therapies (eg, niraparib, capivasertib, [177Lu]Lu-PSMA-617) b. Emerging biomarkers in mHSPC, including PTEN deficiency, HHR mutations, and PSMA positivity i. Compare emerging biomarkers in mHSPC with established biomarker testing guidelines for mCRPC c. Clinical implications of latest data in reshaping the treatment and management of mHSPC d. Introduction of TheraFAQs Reference Guide i. Addressing top-of-mind provider questions on the latest treatment advances and clinical evidence in mHSPC management"

Clinical data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Prostate Cancer • PTEN

The STAMPEDE2 177Lutetium-PSMA-617 (177Lu-PSMA-617) trial: A phase III, randomised, open-label trial in patients with metastatic prostate cancer (mPC) starting androgen deprivation therapy (ADT) (ESMO 2024) - P3 | "SoC includes long-term ADT, androgen receptor signalling inhibitor (ARSI), ± prostate radiotherapy, ± docetaxel as part of 'triplet therapy'...Patients with positive biomarker status are offered a second randomisation into the STAMPEDE2 Niraparib trial...The 177Lu-PSMA-617 trial within the STAMPEDE2 platform protocol is funded by AAA/Novartis, sponsored by University College London (UCL), and co-ordinated by the MRC CTU at UCL. Table: 1658TiP"

Clinical • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Prostate cancer working group 4 (PCWG4) preliminary criteria using serial PSMA PET/CT for response evaluation: Analysis from the PRINCE trial (ESMO 2024) - P1/2 | "We sought to determine reader reproducibility and the clinical correlation of these categories using a trial dataset that incorporated 12-weekly PSMA alongside standard CT / bone scan (PCWG3) assessments. Five experienced nuclear medicine specialists independently reviewed all available PSMA PET/CT scans from the PRINCE trial (NCT03658447; 177Lu-PSMA-617 + pembrolizumab) blinded to conventional imaging response, according to draft PCWG4 criteria. Agreement of PSMA PET/CT response was substantial for all levels of response and almost perfect for PD vs non-PD. The criteria evaluated enable evaluation of level of response (CR, PR, SD) in patients with non-PD by PCWG3 criteria. These criteria detected progression earlier than PCWG3 that correlated well with OS."

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

Recommendations for the dosimetry of patients undergoing therapy with radiopharmaceuticals that include 177Lu. (PubMed, Phys Med) - "Currently the two radiopharmaceuticals approved by the AEMPS that include 177Lu are [177Lu]Lu-DOTA-TATE for the treatment of neuroendocrine tumours and [177Lu]Lu-PSMA-617 for the treatment of mCRPC. This implies that treatments are not planned in advance, but can at least be verified by dosimetry. The purpose of the present document is to provide recommendations for the dosimetry of patients in treatments with the aforementioned radiopharmaceuticals."

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

177Lu-based radioligand therapy: A retrospective multicenter analysis to calculate the effective half-life and follow-up dose for the public. (PubMed, Nuklearmedizin) - "When only measurements up to 48 h p.i. were taken into account the T1/2, eff were shorter (Pluvicto 1.30 d, Lutathera 1.40 d, ihPSMA 1.45 d, ihRRT 1.97 d) compared to 168 h (1.60 d, 1.89 d, 2.10 d, and 2.85 d, respectively). This highlights the need of considering biological clearance mechanisms into calculations of discharge times for patients treated with 177Lu. If direct measurements are not feasible in clinical routine, reference values support inpatient planning while ensuring radiation protection."

Clinical • Journal • Retrospective data