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

Updates on Systemic Treatments for Advanced Pancreatic Neuroendocrine Neoplasm (IASGO 2026) - "Everolimus and sunitinib are established options for progressive disease...Alkylator-based chemotherapy, including streptozotocin/5-FU andcapecitabine/temozolomide, is preferred when substantial tumor shrinkage is required...NETTER-2 established 177Lu-DOTATATE plus octreotide as an important first-line option for newlydiagnosed, SSTR-positive G2/G3 gastroenteropancreatic NETs with a Ki-67 index of 10–55%.Cabozantinib significantly prolonged PFS in previously treated PanNETs in the CABINET trial.Surufatinib is approved in China, while belzutifan is indicated specifically for VHL-associated pNETsnot requiring immediate surgery. For PanNECs, platinum plus etoposide remains the frontline standard, whereas no universallyaccepted salvage regimen exists. Emerging approaches include targeted alpha therapy and DLL3-directed bispecific T-cell engagers, although their roles in PanNENs remain investigational. Futuretreatment will increasingly rely on integrated molecular profiling,..."

Metastases • Endocrine Cancer • Gastrointestinal Neuroendocrine Carcinoma • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Carcinoma • Neuroendocrine Neoplasm • Neuroendocrine Tumor • Solid Tumor • ATRX • DAXX • DLL3 • SSTR • TP53

Clinical Application of Functional Imaging and Peptide Receptor Radionuclide Therapy (IASGO 2026) - "The ongoingphase 3 NETTER-3 trial extends this to newly diagnosed grade 1-2 (Ki-67 <10%) GEP-NET with high tumorburden, comparing Lu-177 DOTATATE plus octreotide LAR with octreotide LAR. Amino acid co-infusion protects the kidneys, but a delayed decline in renalfunction remains the main concern with repeated treatment, so cumulative renal dose should guideretreatment. In Korea, Lu-177 DOTATATE is reimbursed for later-line use and earlier access is beingsought; alpha therapy with Ac-225 DOTATATE (ACTION-1) is the next step for refractory disease."

Clinical • Gastrointestinal Neuroendocrine Tumor • Hematological Disorders • Neuroendocrine Tumor • Solid Tumor • Thrombocytopenia • SSTR

Lutetium-177 radiopharmaceuticals in cancer care: progress and challenges. (PubMed, Front Pharmacol) - "Its clinical relevance is underscored by regulatory approvals of Lutathera® for neuroendocrine tumours and Pluvicto® for metastatic castration-resistant prostate cancer. In addition, heterogeneity in trial design and limited long-term safety data further constrain clinical implementation. We propose a strategic roadmap to advance 177Lu RLT toward a more rigorous, reproducible, and equitable precision oncology framework, emphasising the transition from empiric application to evidence-based personalisation."

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

Phase Ib results from the phase Ib/II study of [177Lu]Lu-DOTA-TATE in combination with standard of care as a first-line treatment for pts with extensive-stage small cell lung cancer. (ASCO 2026) - P1/2 | " Phase Ib was a dosage escalation study to determine the recommended dosage (RD) of 177Lu-DOTATATE – alongside carboplatin AUC 5 + etoposide 100 mg/m2 + anti–programmed cell death protein 1 (PD-1)/PD-L1 therapy (pre/post protocol amendment: tislelizumab 200 mg/atezolizumab 1200 mg, respectively) Q3W in the induction phase, and alongside anti–PD-1/PD-L1 therapy Q3W in the maintenance phase – in pts aged ≥18 y with newly diagnosed SSTR+ (by PET/CT) ES-SCLC. The observed safety profile was consistent with expected toxicity; the RD for Phase II was 7.4 GBq. Safety and preliminary efficacy (N=29). *Most commonly reported: thrombocytopenia (58.6) and anemia (44.8)."

Clinical • Combination therapy • IO biomarker • P1/2 data • Congestive Heart Failure • Heart Failure • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • SSTR • SSTR2

[177Lu]Lu-dota-tate versus sunitinib in patients with metastatic progressive neuroendocrine tumours of the pancreas (OCLURANDOM): a randomised, controlled, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "Using sunitinib as an internal control, our results show clinically significant antitumour efficacy of [177Lu]Lu-dota-tate in pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours, and a better quality of life during the treatment phase. Late adverse events were reported in the [177Lu]Lu-dota-tate group that might affect the tolerance of subsequent lines of treatment."

Journal • P2 data • Cardiovascular • Gastrointestinal Neuroendocrine Tumor • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Neuroendocrine Tumor • Neutropenia • Oncology • Pancreatic Cancer • Septic Shock • Solid Tumor • Thrombosis • 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

Immunogenic cell death as a mechanism of synergy between sunitinib and 177Lu-DOTATATE peptide receptor radionuclide therapy in pancreatic neuroendocrine tumors. (PubMed, Cell Death Discov) - "Intermittent sunitinib combined with ¹⁷⁷Lu-DOTATATE PRRT demonstrated encouraging activity in progressive pNET. The mechanism of synergy in vitro was enhanced ICD, suggesting that immune responses contribute to the synergy in vivo."

Journal • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • CALR • HMGB1 • IL18

CME 6 : PRRT Beyond GEP (EANM 2026) - "Discuss PRRT efficacy as compared to alternative treatment options (e.g. everolimus in case of lung NET)...PRRT has become a recognised treatment option for patients with GEP-NET, the only indication currently covered by EMA approval of 177Lu-DOTATATE. However, preliminary clinical experience suggests that PRRT may also be beneficial in SSTR-expressing NET beyond GEP. This session provides updated knowledge and expertise on the use of PRRT in settings not yet approved by EMA—including lung carcinoids, paraganglioma/pheochromocytoma, meningioma, and medullary thyroid carcinoma—and translates recent updates into clinical practice by identifying tumour- and patient-specific predictors of benefit and risk, and outlining evidence-informed sequencing strategies with systemic therapies and local treatments."

Gastrointestinal Neuroendocrine Tumor • Lung Cancer • Meningioma • Neuroendocrine Tumor • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • SSTR

MOMENTUM-1: Comparing the Radiopharmaceutical Drug, [177Lu]Lu-DOTATATE, to Standard of Care Treatment for Patients With Meningioma That Has Come Back After Prior Treatment (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: RTOG Foundation, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Meningioma • Oncology • Solid Tumor • SSTR2

Phase I trial of M3814 (Peposertib) in combination with lutetium 177 DOTATATE for metastatic well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (ENETS 2026) - P1 | "The combination of oral peposertib with Lu-177 do - tatate is safe, a promising radiation sensitizer in NET patients, and should be investigated in larger randomized clinical trials."

Combination therapy • Metastases • P1 data • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

Dosimetry-Driven Personalization of Radiopharmaceutical Therapies: Evidence and Opportunities. (PubMed, J Nucl Med) - "First-generation RPTs such as 131I-tositumomab (Bexxar) radioimmunotherapy of lymphoma used simplified whole-body dosimetry in each patient to adjust administered activity levels to deal with patient-to-patient heterogeneity of radiation absorbed dose coefficients. In contrast, the commercially successful 177Lu-vipivotide tetraxetan and 177Lu-DOTATATE RPTs are given as one administered-activity-fits-all treatment approach not incorporating patient dosimetry...RPT is evolving rapidly but is generally not curative. We suggest dosimetry will be an important part of the path forward to move RPT from life-prolonging to curative."

Journal • Review • Hematological Malignancies • Lymphoma • Oncology

ETCTN 10450: A phase I trial of peposertib and lutetium 177 DOTATATE in well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). (ASCO-GI 2023) - "In addition, the study will correlate clinical outcome with somatic tumor mutations and germline mutations. Clinical trial information: 04750954."

P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

BH3-mimetic drugs elicit cell death of neuroendocrine tumours in preclinical models – An emerging therapeutic strategy for NETs (ENETS 2025) - "MATERIALS AND METHODS NET patient-derived organoids (PDOs) were established from fresh surgical surplus NET tissue samples and treated with combinations of BH3-mimetics and SOC (Sunitinib, Cabozantinib, Everolimus, and 177Lu-Dotatate)...Finally, we show that combining Navitoclax with Cabozantinib or 177Lu-Dotatate results in marked cell death of NETs, while the single treatments exhibited a significantly lower effect. CONCLUSION Overall, this study showed that the survival of NETs depends on the activity of the Bcl-2 family of proteins and that their inhibition using BH3-mimetics combined with the SOC leads to cell death in patient-derived preclinical models. Our data warrant the investigation of BH3-mimetics with the SOC for patients with NETs as a novel therapeutic approach."

IO biomarker • Preclinical • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • BCL2 • BCL2L1 • MCL1

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

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

Transitioning from CA to NCA 177Lu in the preparation of [177Lu]Lu-DOTATATE for PRRT - observations and considerations from a retrospective review. (PubMed, Phys Eng Sci Med) - "Observed differences in SUV are likely due to variations in administered peptide mass (due to formulation differences and SSA treatment) leading to competition for receptors between radiolabelled [177Lu]Lu-DOTATATE and 'cold' peptide. The optimisation of peptide mass has the potential to minimise radiation dose to healthy tissue and organs."

Journal • Retrospective data • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Pancreatic 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

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

Pharmacokinetics and RP2D analysis from ETCTN 10388: A phase I trial of triapine and lutetium Lu-177 dotatate in well-differentiated somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). (ASCO-GI 2023) - "The RP2D of triapine is 150 mg QD on days 1-14 in combination with Lu-177 DOTATATE on day 1 of every 56-day cycle. Clinical trial information: 04234568."

P1 data • PK/PD data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

A phase II randomized control trial of triapine plus lutetium 177 DOTATATE versus lutetium 177 DOTATATE alone for well-differentiated somatostatin receptor-positive neuroendocrine tumors. (ASCO 2024) - P1 | "Secondary endpoint is to evaluate median PFS. We are also evaluating triapine PK, plasma deoxyribonucleosides, circulating DNA and plasma hPG80, a novel blood based diagnostic biomarker."

Clinical • P2 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • SSTR

Profiling proteomic responses in small intestinal neuroendocrine tumor GOT1 after [177Lu]Lu-DOTATATE therapy. (PubMed, BMC Cancer) - "[177Lu]Lu-DOTATATE therapy induced extensive proteomic changes in GOT1 tumors, including suppression of pathways associated with invasiveness and modulation of p53- and stress-related signaling. These findings suggest potential therapeutic benefits of combining [177Lu]Lu-DOTATATE with agents targeting p53 regulation or endoplasmic reticulum stress pathways to improve treatment efficacy in neuroendocrine tumors."

Journal • Neuroendocrine Tumor • Oncology • Solid Tumor • Targeted Protein Degradation • RHOA • SSTR

Pregnancy in a patient with metastatic functioning midgut neuroendocrine tumor receiving lanreotide after peptide receptor radionuclide therapy. (PubMed, Arch Endocrinol Metab) - "The patient had previously undergone treatment with 177Lu-DOTATATE, debulking surgery, and lanreotide therapy...This case highlights important clinical considerations regarding the continuation of somatostatin analog therapy, biochemical monitoring, peri-delivery planning for a carcinoid crisis, and pregnancy after peptide receptor radionuclide therapy in patients with functioning metastatic NETs. It provides supportive observational evidence that the continuation of lanreotide during pregnancy may be feasible in carefully selected patients under close multidisciplinary supervision, although conclusions regarding safety remain limited by the rarity of available data."

Journal • Acromegaly • Carcinoid Syndrome • Carcinoid Tumor • Endocrine Cancer • Endocrine Disorders • Neuroendocrine Tumor • Oncology • Solid Tumor

Radioligand therapies for recurrent meningiomas - 177Lu-Dotatate, 68Ga-Dotatate and the MOMENTUM-1 study (SNO 2026) - No abstract available

Brain Cancer • Meningioma • Solid Tumor

Effective treatment of carcinoid syndrome with peptide receptor radionuclide therapy. (PubMed, Endokrynol Pol) - No abstract available

Journal • Carcinoid Syndrome • Neuroendocrine Tumor • Oncology • Solid Tumor

177Lu-FAPI-2286 Radioligand Therapy in Refractory Scalp Melanoma. (PubMed, Clin Nucl Med) - "A 66-year-old man with inoperable malignant scalp melanoma, refractory to immunotherapy, underwent 99mTc-HYNIC-TOC SPECT/CT for evaluating the possibility of radioligand therapy with 177Lu-DOTATATE, which demonstrated no tracer uptake in scalp lesions, precluding 177Lu-DOTATATE therapy...After 4 cycles of treatment, all lesions showed regression and he was referred for tumor resection. This case illustrates the clinical utility of FAPI-based theranostic and shows 99mTc-FAPI SPECT/CT can directly inform targeted radioligand therapy using 177Lu-FAPI, thereby expanding therapeutic options in melanoma management."

Journal • Melanoma • Oncology • Solid Tumor