Lutathera (lutetium Lu 177 dotatate) / Novartis - LARVOL DELTA

177Lu-DOTATATE versus high-dose long-acting octreotide for somatostatin receptor-positive advanced GEP-NETs: A multicenter, randomised, open-label, positive-controlled phase III study (ESMO Asia 2025) - P3 | "177Lu-DOTATATE had an acceptable safety profile in GEP-NETs pts with PFS improvement versus high-dose long-acting octreotide."

Clinical • Late-breaking abstract • Metastases • P3 data • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • SSTR

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

The South Australian 177Lu-DOTATATE peptide receptor radionuclide therapy service: an 11-year review of toxicity, health-related quality of life, and survival. (PubMed, ESMO Gastrointest Oncol) - "Median duration of follow-up was 37.6 months (range 0.0-134.6 months) with a median OS from first cycle of PRRT 48.4 months (95% confidence interval 42.5-57.3 months). Patients with advanced NEN/NET or other somatostatin receptor-positive malignancies treated with 177Lu-DOTATATE at our centre had improved hr-QoL following iPRRT, with comparable toxicity and OS to other centres."

HEOR • Journal • Endocrine Cancer • Hematological Disorders • Hematological Malignancies • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

Multi-center NCI-sponsored phase I study of triapine in combination with 177Lu-dotatate in patients with well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NETs) (ESMO 2025) - P1 | "Triapine (150 mg) is the RP2D. A randomized phase 2 trial (ETCTN 10558) comparing the combination to 177Lu-dotatate monotherapy is currently enrolling at 14 sites across the United States."

Clinical • Combination therapy • P1 data • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Somatostatin analogue continuation upon progression in patients with gastroenteropancreatic neuroendocrine tumour (SAUNA trial): a randomised controlled trial protocol. (PubMed, BMJ Open) - P4 | "Second-line treatment options include targeted therapy (everolimus or sunitinib), or peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. Results of the study will be published in peer-reviewed international journals and presented at international conferences. NCT05701241."

Clinical protocol • Journal • Endocrine Cancer • Gastrointestinal Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

A Study of [177Lu]Lu-DOTA-TATE in Newly Diagnosed ES-SCLC Patients in Combination With Carboplatin, Etoposide and Atezolizumab (clinicaltrials.gov) - P1/2 | N=24 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | N=140 ➔ 24

Enrollment change • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Atypical presentation and association of medullary thyroid carcinoma: reports from a tertiary care center in Northwest India. (PubMed, Endocrinol Diabetes Metab Case Rep) - "The standard management remains surgical resection, with tyrosine kinase inhibitors (TKIs) in RET mutation-positive or RET mutation-negative metastatic cases and/or Lutathera peptide receptor radionuclide therapy (PRRT) used in disseminated disease, and external beam radiotherapy for locally aggressive or infiltrative retaining a limited role...Of the 80 MTC patients reviewed, this case series highlights 10 atypical presentations in nine cases : 3 unusual tumors along with MTC, namely chondrosarcoma, carcinoma prostrate, and ectopic Cushing's syndrome; 4 unusual associations or presenting manifestations: pneumoconiosis masquerading as lung metastasis, Marfanoid habitus in MEN-2A and VHL spectrum disease, 1 with skull metastasis, and 2 cases with TKI-related complications in the form of glomerulonephritis and one patient displayed Marfanoid habitus with a RET mutation but without MEN2B or fibrillin gene mutation, while another developed bowel perforation secondary to..."

Journal • Cushing’s Disease • Endocrine Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Oncology • Prostate Cancer • Respiratory Diseases • Sarcoma • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Von Hippel-Lindau Syndrome • RET

177Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumors: A systematic review and meta-analysis (Frontiers) - "A total of 14 studies with 1844 patients were included. The pooled disease control rate (DCR) was 87.6% (95% Confidence Interval (CI), 82.5%-92%), and the objective response rate (ORR) was 32.2% (95% CI, 25.4%-39.3%). Median progression-free survival (PFS) was 30.87 months (95% CI, 22.71–39.04), and median overall survival (OS) was 51.85 months (95% CI, 39.99–63.71)....PFS was longer in pancreatic NETs 93.9 months (95% CI, 39.45–148.35) than in gastrointestinal NETs 66.32 months (95% CI, 41.78–90.87)....177Lu-DOTA-Tyr3-octreotate (177Lu-DOTATATE) demonstrates high efficacy and a favorable safety profile in treating NETs."

Review • Neuroendocrine Tumor • Pancreatic Cancer

177Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial. (PubMed, J Nucl Med) - "On the basis of the findings, we recommend a starting dose of 200 mg BID for future studies, with the potential to escalate to 300 mg BID depending on patient tolerance. Further investigation in larger, randomized trials is warranted to assess the clinical efficacy of this combination and optimize dosing strategies."

Journal • P1 data • Endocrine Cancer • Fatigue • Hematological Disorders • Lung Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • Thrombocytopenia • SSTR

Safety, tolerability and efficacy of 212 Pb-DOTAMTATE as a targeted alpha therapy for subjects with unresectable or metastatic somatostatin receptor-expressing gastroenteropancreatic neuroendocrine tumors (SSTR+ GEP-NETs): A phase 2 study. (ASCO 2024) - P2 | "Research Funding: No funding sources reported. In PRRT-naïve subjects with SSTR+ unresectable or metastatic GEP-NETs treatment with up to 4 cycles of ²¹²Pb-DOTAMTATE (67.6 μCi/kg/cycle) was well-tolerated, with a safety profile consistent with the underlying disease and expected toxicities of radioligand therapy, similar to 177 Lu-DOTATATE. The ORR of 47.2% in cohort 1 (50% in the pooled dataset) appears to be substantially higher than the ORR previously reported for 177 Lu-DOTATATE in the pivotal NETTER-1 study (ORR 18% (10–25%))."

Clinical • Metastases • P2 data • Carcinoid Syndrome • Endocrine Cancer • Hematological Disorders • Infectious Disease • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Septic Shock • Solid Tumor • SSTR

Lutathera: Regulatory submission for gastroenteropancreatic neuroendocrine tumors in 2028 (SECFilings.com) - Q4 & FY2025 Results

Filing • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Pancreatic Neuroendocrine Tumor

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

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

Neo-adjuvant systemic radiation therapy for inoperable hepatic hilum neuroendocrine tumor with 177Lu- DOTATATE: successful final surgical resection. (PubMed, Asia Ocean J Nucl Med Biol) - "Due to residual involvement of the common hepatic duct and right portal vein margins, two additional cycles of adjuvant 177Lu-DOTATATE were administered post-surgery. Long-term follow-up imaging over a 20-month period has demonstrated stable disease, emphasizing the potential benefits of incorporating neoadjuvant and adjuvant 177Lu-DOTATATE in selected NET cases."

Journal • Neuroendocrine Tumor • Oncology • Solid Tumor

A phase II study of lutetium-177 DOTATATE in metastatic prostate cancer with neuroendocrine differentiation. (ASCO-GU 2026) - P2 | "Clinical Trial Registry Number: NCT05691465. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Metastases • P2 data • Genito-urinary Cancer • 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

Combination therapy strategies in engineered 177Lu radiopharmaceuticals beyond single modality: design principles and application outlet. (PubMed, Cell Commun Signal) - "Since the U.S. Food and Drug Administration (FDA) approved [177Lu]Lu-DOTA-TATE in 2018, 177Lu-based radiopharmaceuticals have demonstrated significant clinical value in the targeted treatment of neuroendocrine tumors (NETs) and prostate cancer...Combination therapy has therefore emerged as a promising strategy to address these obstacles. This review provides a systematic overview of the preparation techniques, clinical efficacy, and combination therapy approaches involving 177Lu radiopharmaceuticals, with the aim of offering a theoretical foundation and practical guidance for optimizing therapeutic paradigms."

Journal • Review • Genito-urinary Cancer • Genitourinary Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor

ETCTN 10388: a first in human phase I trial of triapine and lutetium Lu 177 DOTATATE in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (AACR 2023) - P1 | "The combination of triapine and Lu-177 DOTATATE was safe with preliminary efficacy signals, which will be further evaluated in ETCTN 10558, a randomized phase 2 study that is comparing the effectiveness of triapine and Lu-177 DOTATATE to Lu-177 DOTATATE alone."

P1 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Cumulative Absorbed Dose and Successive Cyclic Reduction in Absorbed Dose Predict Response to 177Lu-DOTATATE in Neuroendocrine Tumors. (PubMed, J Nucl Med) - P=N/A | " Both AD and changes in AD/AA were independently associated with radiologic response to [177Lu]Lu-DOTATATE in patients with neuroendocrine tumors. The consistent decrease in AD/AA over a course of therapy suggests a potential imaging biomarker that could inform adaptive treatment strategies, which should be further evaluated in a prospective setting and considered when designing dosimetry-guided [177Lu]Lu-DOTATATE trials."

Journal • Neuroendocrine Tumor • Oncology • Solid Tumor

[177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study. (ASCO-GI 2024) - P3 | "177Lu-DOTATATE significantly prolonged PFS and demonstrated a clinically meaningful ORR, compared with high-dose octreotide LAR, in pts with newly diagnosed advanced G2 and G3 GEP-NETs. Safety was in line with the established profile of 177Lu-DOTATATE. This is the first randomized study to demonstrate efficacy of RLT as 1L treatment in any malignancy and will change clinical practice."

Clinical • Late-breaking abstract • Metastases • P3 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

RYZ101 (225Ac-DOTATATE) + Carboplatin + Etoposide + Atezolizumab in Somatostatin Receptor Expressing Extensive-Stage Small-Cell Lung Cancer (IASLC-WCLC 2024) - P1 | "Preliminary pharmacokinetic findings indicate clearance and half-life comparable to previous studies of RYZ101 and 177 Lu-DOTATATE. Conclusions : There were no DLTs reported at DL1 (6.5 MBq) and the dose of RYZ101 has been escalated to the next dose level. The study is actively enrolling patients to receive RYZ101 at DL2 (8.3 MBq) and additional safety data will be presented once mature."

Back Pain • Cardiovascular • Fatigue • Heart Failure • Hematological Disorders • Infectious Disease • Influenza • Lung Cancer • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • SSTR • SSTR2

First-line efficacy of [177Lu]Lu-DOTA-TATE in patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors by tumor grade and primary origin: Subgroup analysis of the phase III NETTER-2 study (ESMO-GI 2024) - P3 | "This preplanned subgroup analysis examined efficacy by NET grade (G2, G3) and NET origin (pancreas, small intestine [SI]). Pts were randomized to receive 4 cycles of 177Lu-DOTATATE (4 × 7.4 GBq) + 30 mg octreotide long-acting release (LAR) every 8 weeks (Q8W) during 177Lu-DOTATATE treatment then Q4W (177Lu-DOTATATE arm; n=151), or 60 mg octreotide LAR Q4W (control arm; n=75). 1L 177Lu-DOTATATE efficacy was maintained across NET grades (G2, G3) and locations (pancreas, SI) and it should be considered a standard of care for this pt population."

Clinical • Metastases • P3 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jan 2027 ➔ Jan 2033 | Trial primary completion date: Jan 2026 ➔ Jan 2030

Trial completion date • Trial primary completion date • Endocrine Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor • NF1 • SSTR • VHL

Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study. (PubMed, Br J Surg) - "Neoadjuvant treatment with 177Lu-DOTATATE is safe and effective for patients with NF-PanNETs."

Journal • P2 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

Phase II Study of 177Lu-DOTATATE for Progressive Metastatic Pheochromocytomas and Paragangliomas: Interim Analysis of Efficacy, Safety, and Biomarkers. (PubMed, J Clin Oncol) - "177Lu-DOTATATE demonstrated effectiveness and acceptable safety profile for progressive, metastatic PPGL. CRS may occur but can be mitigated through pretreatment with antihypertensives, and, when appropriate, intensified monitoring in the ICU with intravenous antihypertensives."

Biomarker • Journal • P2 data • Critical care • Oncology • Solid Tumor • CHGA • SSTR