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

Testing the Addition of An Anti-cancer Drug, M3814 (Peposertib), to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Pancreatic Neuroendocrine Tumors (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Jun 2026 | Trial primary completion date: Oct 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Endocrine Cancer • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Solid Tumor

Lutetium-177 dotatate PRRT in GEP-NETs: Hematologic toxicity trends, recovery profiles, and discontinuation rates (ASH 2025) - "Lutetium-177 DOTATATE PRRT demonstrates an excellent hematologic safety profile in GEP-NET patients. Severe cytopenias are uncommon, predominantly transient, and rarely necessitate treatment discontinuation. These findings support the continued use of PRRT in appropriate candidates, with cytopenia-related discontinuation occurring in fewer than 3% of cases."

Gastrointestinal Neuroendocrine Tumor • Hematological Disorders • Hematological Malignancies • Neuroendocrine Tumor • Pancreatic Cancer • Solid Tumor

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

Clinical outcomes of [177Lu]Lu-DOTA-TATE (177Lu-DOTATATE) vs everolimus (EVE) in managing patients (pts) with gastroenteropancreatic-neuroendocrine tumors (GEP-NETs): Real-world analysis of the PRIME initiative. (ASCO-GI 2026) - "Funded by Novartis Pharmaceuticals Corporation The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Clinical data • Real-world • Real-world evidence • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Retreatment patterns and outcomes in patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with [177Lu]Lu-DOTA-TATE (177Lu-DOTATATE): A PRIME real-world study. (ASCO-GI 2026) - "Funded by Novartis Pharmaceuticals Corporation The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Real-world • Real-world evidence • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Phase I study of fulvestrant in combination with 177Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. (ASCO-GI 2026) - P1 | "Funded by University of Chicago Internal Cancer Center Funding Clinical Trial Registration Number: NCT06663072 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Combination therapy • Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Enhancing PRRT Outcome Prediction in Neuroendocrine Tumors: Aggregated Multi-Lesion PET Radiomics Incorporating Inter-Tumor Heterogeneity. (PubMed, Cancers (Basel)) - "This study demonstrates that informed lesion selection and tailored aggregation strategies significantly impact the predictive performance of radiomics-based models for progression and TTP prediction in PRRT-treated NET patients. These approaches can potentially enhance model accuracy and better capture tumor heterogeneity, supporting more personalized and practical PRRT implementation."

Heterogeneity • Journal • Neuroendocrine Tumor • Oncology • Solid Tumor

Treating Pediatric Oncology Patients: The Emerging Role of Radioligand Therapy. (PubMed, Cancers (Basel)) - "Recently, radioligand therapy (RLT) consisting of a radionuclide attached to a ligand, such as [177Lu]Lu-DOTA-TATE, has been approved for the treatment of NETs in adolescents aged ≥12 years...Future research is needed to assess potential combinations of RLTs with conventional chemotherapy and radiation sensitizers in order to optimize the treatment for pediatric patients with NETs. This review highlights the current status and future directions for RLTs as theranostics for pediatric patients with NETs and neuroblastomas."

Journal • Review • Neuroblastoma • Neuroendocrine Tumor • Oncology • Pediatrics • Solid Tumor

Inter-institutional variability in kidney dosimetry during 177Lu-DOTATATE therapy in Japan. (PubMed, Radiol Phys Technol) - "Voxel-based dosimetry can mitigate inter-institutional variability independent of contouring. Our findings emphasize the importance of algorithm standardization for reliable 177Lu-DOTATATE kidney dosimetry in Japan."

Journal

Challenges and Opportunities in Radioligand Therapy. (PubMed, J Nucl Med Technol) - "Although radioiodine provides the historical foundations of theranostics, the prototype RLTs include 68Ga-DOTATATE and 177Lu-DOTATATE, which target somatostatin receptor subtype 2 in neuroendocrine tumors, and 68Ga-PSMA-617 and 177Lu-PSMA-617, which target prostate cancer. RLT, weaponized in cancer management through advances in instrumentation and radiochemistry, is transforming the nuclear oncology landscape. Equitable access to these advanced tools remains a global consideration."

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

Advancements in Targeted Radiopharmaceuticals: Innovations in Diagnosis and Therapy for Enhanced Cancer Management. (PubMed, Chembiochem) - "Clinically approved agents, such as 177Lu-DOTATATE and 177Lu-PSMA-617, are used for neuroendocrine tumors and metastatic castration-resistant prostate cancer, respectively, with significant therapeutic efficacy. The potential avenues include theranostics, predictive modeling for patient selection, and new molecular targeting strategies. This review highlights the transformative potential of RPhs in precision oncology, providing an overview of the current clinical applications and future research trajectories toward improved cancer management."

Journal • Review • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • CXCR4 • GRP-10

Results of a single-arm, open-label, multicenter phase 2 study of the radiopharmaceutical [177Lu]Lu-DOTA-TATE in adults with advanced intracranial meningioma (SNO 2025) - P2 | "Treatment with SSTR2-targeting 177Lu-Dotatate is well tolerated and 69% of patients achieved PFS-6, comparing favorably to historical benchmarks. 177Lu-Dotatate therefore may be a useful new therapeutic modality for patients with advanced meningiomas and will be further explored in MOMENTUM-1 (NCT06955169), an open-label, randomized, phase 2 trial."

Clinical • Metastases • P2 data • Brain Cancer • Hematological Disorders • Meningioma • Neuroendocrine Tumor • Solid Tumor • Thrombocytopenia • SSTR • SSTR2

[68Ga]Ga-DOTA-TATE PET as imaging biomarker for response assessment and monitoring in patients receiving [177Lu]Lu-DOTA-TATE for advanced intracranial meningioma (SNO 2025) - P2 | "68Ga-Dotatate PET is a promising imaging biomarker in patients with advanced meningioma. Treatment with 177Lu-Dotatate led to substantial reduction in SUVR (lesion/SSS) in a subset of patients. In contrast to other reports, 68Ga-Dotatate assessments were generally concordant with post-gad T1 based MRI assessments per RANO."

Biomarker • Clinical • Metastases • Brain Cancer • Meningioma • Solid Tumor • SSTR • SSTR2

Targetable somatostatin receptor expression assessed by DOTATATE PET imaging in children and young adults with recurrent/progressive high-risk central nervous system (CNS) tumors: Initial screening results from the CONNECT2007 Lutathera Phase I/II trial (SNO 2025) - P1/2 | "Preliminary CONNECT2007 screening results provide insight into the prevalence and heterogeneity of targetable SST2A expression across high-risk pediatric and young adult CNS tumors. Strong DOTATATE uptake was identified in all patients with progressive meningiomas, some patients with medulloblastoma (particularly group 3 and SHH, TP53-mutant), and rarer high-grade glioneuronal tumors, suggesting a potential role for SST2A-targeted theranostics in these entities."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Ependymoma • Glioneuronal Tumor • Medulloblastoma • Meningioma • Oncology • Pineoblastoma • Solid Tumor • BAP1 • BCOR • CHEK2 • SHH • SSTR • TP53

Combination lutetium Lu 177 dotatate for refractory meningioma (SNO 2025) - "This distinguishing feature diverges from other targeted approaches for meningiomas, which are reliant on specific driver mutations, which occur in lower frequency in which these individual mutations occur (NF2 43-55%, SMO 3-5%, PIK3 4.5%, AKT1 9%). We present two cases of patients with refractory meningioma treated with combination Lutathera and octreotide."

Brain Cancer • Meningioma • Neuroendocrine Tumor • Pancreatic Cancer • Solid Tumor • AKT1 • SMO • SSTR • SSTR2

MOMENTUM-1: a multicenter, randomized, open-label, phase 2 study of [177Lu]Lu-DOTA-TATE in adults with progressive grade 1-3 meningioma (RTOG 3523) (SNO 2025) - "MOMENTUM-1 is a multicenter, randomized, open-label, phase II study of 177Lu-Dotatate in adult patients with progressive WHO grade 1-3 meningioma. This clinical trial is expected to start enrolling patients in the United States in the third quarter of 2025. Details on study design, eligibility criteria for subject enrollment and study site eligibility criteria will be presented."

Clinical • P2 data • Brain Cancer • Meningioma • Neuroendocrine Tumor • Solid Tumor • SSTR • SSTR2

Targetable somatostatin receptor expression assessed by DOTATATE PET imaging in children and young adults with recurrent/progressive high-risk central nervous system (CNS) tumors: Initial screening results from the CONNECT2007 Lutathera Phase I/II trial (SNO 2025) - P1/2 | "Preliminary CONNECT2007 screening results provide insight into the prevalence and heterogeneity of targetable SST2A expression across high-risk pediatric and young adult CNS tumors. Strong DOTATATE uptake was identified in all patients with progressive meningiomas, some patients with medulloblastoma (particularly group 3 and SHH, TP53-mutant), and rarer high-grade glioneuronal tumors, suggesting a potential role for SST2A-targeted theranostics in these entities."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Ependymoma • Glioneuronal Tumor • Medulloblastoma • Meningioma • Oncology • Pineoblastoma • Solid Tumor • BAP1 • BCOR • CHEK2 • SHH • SSTR • TP53

Results of a single-arm, open-label, multicenter phase 2 study of the radiopharmaceutical [177Lu]Lu-DOTA-TATE in adults with advanced intracranial meningioma (SNO 2025) - P2 | "Treatment with SSTR2-targeting 177Lu-Dotatate is well tolerated and 69% of patients achieved PFS-6, comparing favorably to historical benchmarks. 177Lu-Dotatate therefore may be a useful new therapeutic modality for patients with advanced meningiomas and will be further explored in MOMENTUM-1 (NCT06955169), an open-label, randomized, phase 2 trial."

Clinical • Metastases • P2 data • Brain Cancer • Hematological Disorders • Meningioma • Neuroendocrine Tumor • Solid Tumor • Thrombocytopenia • SSTR • SSTR2

Outcomes of Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in Patients with Metastatic Pheochromocytoma and Paraganglioma. (PubMed, J Nucl Med) - " Our findings suggest that PRRT remains a therapeutic strategy for mPPGL, is well-tolerated, and may improve cancer-related symptoms. Large-scale prospective studies are needed to validate structural responses and durability."

Journal • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hypertension • Leukopenia • Myelodysplastic Syndrome • Oncology • Solid Tumor • Thrombocytopenia

Update on Systemic Therapies for Metastatic/Unresectable Pheochromocytomas and Paragangliomas and Future Directions. (PubMed, Cancers (Basel)) - "Radiopharmaceuticals such as 131I-MIBG and 177Lu-DOTATATE continue to play a pivotal role, achieving disease control in many patients. Cytotoxic regimens, particularly temozolomide, remain relevant, with some studies suggesting that SDHB-mutated PPGLs demonstrate a heightened sensitivity associated with MGMT promoter hypermethylation and reduced MGMT expression. Targeted agents are increasingly important: multi-kinase inhibitors such as sunitinib, anlotinib, and cabozantinib have shown meaningful activity. The landmark approval of belzutifan, a HIF-2α inhibitor, in 2025 represents the first oral targeted therapy for advanced/metastatic PPGL, which is particularly relevant for pseudohypoxic Cluster 1 tumors...This review summarizes current evidence and highlights ongoing clinical trials, underscoring a paradigm shift toward precision medicine and rational combination strategies. Collectively, these advances bring cautious optimism that metastatic PPGLs may soon become a..."

IO biomarker • Journal • Review • Endocrine Cancer • Oncology • Solid Tumor • EPAS1 • MGMT • SDHB

Efficacy and Safety of Non-Surgical Treatments for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. (PubMed, Pharmaceuticals (Basel)) - "Targeted therapies showed modest objective response rates (ORRs) but high disease control rates (DCRs): everolimus (ORR 7%, 95% CI: 3-10%; DCR 81%, 95% CI: 75-87%), sunitinib (ORR 12%, 95% CI: 5-19%; DCR 79%, 95% CI: 70-88%), surufatinib (ORR 19%, 95% CI: 12-27%; DCR 81%, 95% CI: 73-89%). Cytotoxic chemotherapy demonstrated higher ORRs: dacarbazine-based (32%, 95% CI: 21-43%), streptozocin-based (40%, 95% CI: 25-54%), temozolomide-based (42%, 95% CI: 29-55%). PRRT showed varying efficacy: 177Lu-DOTATATE (ORR 36%, 95% CI: 27-44%; DCR 84%, 95% CI: 76-92%), 90Y-DOTATOC (ORR 27%, 95% CI: 18-36%; DCR 73%, 95% CI: 63-83%)...Immunotherapy with pembrolizumab showed limited efficacy (ORR 7%, 95% CI: 0-14%)...PRRT also shows robust antitumor activity and disease control, while SSAs and targeted therapies are effective treatment options for disease stabilization. Immunotherapy demonstrated limited antitumor activity, and further research is needed to establish its role in pNET..."

Clinical • Journal • Retrospective data • Review • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor

Radiosensitization of NET cells by HSP90 inhibitor ganetespib is mediated through pleiotropic stress responses. (PubMed, EJNMMI Res) - "Given the lack of significant effects on direct DNA repair or transcriptomic responses, our findings suggest that HSP90 inhibition radiosensitizes NET cells by inducing a pleiotropic effect on multiple stress-related pathways at the protein level, rather than solely through disruption of DNA damage response mechanisms. This effect is likely driven by loss of HSP90 function and subsequent cumulated unfolded protein and proteotoxic stress."

Journal • Neuroendocrine Tumor • Oncology • Solid Tumor • CDC37 • RAD51 • SSTR • SSTR2 • TP53BP1

LANTana: Lutathera and ASTX727 in Neuroendocrine Tumours (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: Imperial College London | Trial completion date: Dec 2025 ➔ Feb 2029 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Neuroendocrine Tumor • Solid Tumor

Peptide-Drug Conjugates in Tumor Therapy: Current Advances and Future Perspectives. (PubMed, Cancer Lett) - "Currently, the PDC Lutathera has been approved by the U.S. FDA for the treatment of cancer, and several other PDCs candidates are currently under investigation in clinical trials...Additionally, the therapeutic advantages, existing challenges and future clinical applications of PDCs are also discussed. This review tries to offer critical insights into PDCs and provides new perspectives for the future development of antitumor therapies."

Journal • Review • Oncology

[68Ga]Ga-DOTA-TATE PET as imaging biomarker for response assessment and monitoring in patients receiving [177Lu]Lu-DOTA-TATE for advanced intracranial meningioma (WFNOS 2025) - P2 | "68Ga-Dotatate PET is a promising imaging biomarker in patients with advanced meningioma. Treatment with 177Lu-Dotatate led to substantial reduction in SUVR (lesion/SSS) in a subset of patients. In contrast to other reports, 68Ga-Dotatate assessments were generally concordant with post-gad T1 based MRI assessments per RANO."

Biomarker • Clinical • Metastases • Brain Cancer • Meningioma • Oncology • Solid Tumor • SSTR • SSTR2