Solucin (177Lu-edotreotide)

P3, N=202, Recruiting, ITM Solucin GmbH | Trial completion date: Sep 2026 --> Sep 2027 | Trial primary completion date: Sep 2024 --> Jun 2027

P3, N=300, Active, not recruiting, Lund University Hospital | Not yet recruiting --> Active, not recruiting

P3, N=309, Active, not recruiting, ITM Solucin GmbH | Trial completion date: Jun 2029 --> Dec 2029 | Trial primary completion date: Jun 2024 --> Dec 2024

P3, N=120, Recruiting, Grupo Espanol de Tumores Neuroendocrinos | Not yet recruiting --> Recruiting | Initiation date: Jul 2023 --> Oct 2023

P2, N=100, Not yet recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Only ten patients experienced grade ≥ 3 myelosuppression (3% of all patients). The observed safety profiles and favorable therapeutic responses demonstrated the potential of Lu-iPSMA and Lu-DOTATOC to improve overall survival and quality of life in patients with progressive and advanced mCRPC and NET.

P3, N=120, Not yet recruiting, Grupo Espanol de Tumores Neuroendocrinos

IART with 177 Lu-DOTATATE significantly increases tumour dose while reducing overall systemic toxicity in comparison to SRT treatment. After considering the maximum tolerance limit of kidneys in peptide receptor radionuclide therapy, the number of treatment cycles and injected activity can be optimized further with IART for better response and survival.

Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of GEP-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting (CTPM) in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included: 1) PRRT re-treatment; 2) PRRT and immunotherapy combinations; 3) PRRT and DNA damage repair inhibitor combinations; 4) Treatment for liver dominant disease; 5) Treatment for PRRT resistant disease; and 6) Dosimetry modified PRRT.

Our results showed that disturbing the cell redox balance using a GSH synthesis inhibitor increased Lu-DOTATATE efficacy without additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with Lu-DOTATATE.

In our study, we showed that SUVmax/Sx, RECIST, ∆TDTV + new lesion, and ∆TTLD + new lesion parameters can predict OS in the evaluation of response to treatment.

The aim of this critical review is to summarize current literature evidence assessing the role of Lutathera outside the approved indications. Moreover, ongoing clinical trials evaluating new possible applications of Lutathera will be considered and discussed to provide an updated picture of future investigations.

We developed a translatable radioimmunotherapy platform that incorporates a FDA-approved theranostic endoradiotherapy (Lutathera) to improve tumor response to CAR-T cell therapy. The next steps would be to explore the immunomodulatory effects of low-dose radiation systematically and elucidate the mechanism of action.

Recent success of radiotheranostic agents such as 177Lu-DOTATATE and 177Lu-PSMA617 heralds the vibrant expansion of radiotheranostics. We developed an ANTXR1 targeting peptide conjugated with DOTA for radiotheranostics. We found that PC01 demonstrated favorable biodistribution and specific in vitro/ in vivo binding to ANTXR1, which prompts us to further optimize and develop a peptide-based ANTXR1 targeting radiotheranostic agent.Ref 1. Cancer Res (2022) 82 (12_Supplement): 5007

P2, N=0, Withdrawn, Excel Diagnostics and Nuclear Oncology Center | N=50 --> 0 | Recruiting --> Withdrawn

Guidelines generally refer to peptide receptor radionuclide therapy as a second-line therapy after SSA in gastroenteric and second- or third-line therapy in pancreatic NETs to improve survival rates and quality of life. Although we do not have sufficient data, 177Lu-DOTA-TATE therapy may also have a role in high-grade NET therapy, mostly in combination with other treatments such as chemotherapy.

All lesions demonstrated 68Ga-DOTATATE PET/CT uptake, and the patient received 4 peptide receptor radionuclide therapy cycles with 177Lu-DOTATATE, with pronounced reduction in the size of the liver, cardiac, and pleural lesions. This is the first case to demonstrate partial response to peptide receptor radionuclide therapy in metastatic thymoma, thus suggesting possible treatment option to refractory and advancing metastatic thymoma.

We report an updated and solid estimate of DCR achieved with 177Lu- and 90Y-PRRT in PCCs and PGLs, showing that these therapies can be considered in the multidisciplinary treatment of PCCs and PGLs as alternatives to I-131 MIBG and chemotherapy.

99mTc-imaging of RP-2, as compared to RP-1, had better efficiency and sensitivity and could effectively be used as an alternative to Ga-68 DOTA/TOC PET imaging and Lu-177 DOTA-TATE PRRT therapy response evaluation.

Peptide receptor radionuclide therapy with 177Lu-DOTATATE is now frequently included in the management of neuroendocrine neoplasms, with prospective randomized control studies demonstrating its beneficial impact on survival and quality of life. Nonetheless, peptide rector radionuclide therapy is still considered palliative rather than curative and may be accompanied by adverse effects.

P1, N=10, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

P2, N=25, Not yet recruiting, National Cancer Institute (NCI)

P1, N=24, Not yet recruiting, National Cancer Institute (NCI)

PRRT is now considered an effective and safe treatment option for SSTR-expressing NET: following the approval of 177Lu-DOTATATE by FDA and EMA, PRRT is now part of the therapeutic algorithms of the main scientific societies. Recently, several emerging radiopharmaceuticals showed encouraging results for both imaging and therapy (eg, SSTR-analogues labelled with 18F, SSTR-antagonists for both diagnosis and therapy, alpha-labelling for therapy, radiopharmaceuticals binding to new cellular targets). Aim of this review is to focus on current knowledge and to outline emerging perspectives for NEN's diagnosis and therapy.

P2, N=32, Recruiting, Nicholas Fidelman, MD | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2022 --> Dec 2023

Our prospective, randomized controlled study may lead to new recommendations for the use of Lutathera® in patients with intestinal progressive NET, and should confirm that four cycles will be more effective than two, with limited adverse impact on safety. Four Lutathera® treatment cycles have the potential to prolong life and improve quality of life in patients.

Treatment of NET patients with PRRT requires dedicated clinical expertise due to the biological characteristics of PRRT and specific characteristics of NET patients. This review provides an overview for clinicians dealing with NET on the history, molecular characteristics, efficacy, toxicity and relevant clinical specifics of PRRT.

P3, N=37, Completed, Jules Bordet Institute | Unknown status --> Completed | Trial completion date: Jan 2020 --> Sep 2022 | Trial primary completion date: Jun 2019 --> Jan 2022

METHODS To determine the anti-proliferative effects of VPA, Decitabine and the combination of both, all cell lines were treated for 72 hours and an MTT assay was used to determine the IC50. Furthermore, treatment of non-neuroendocrine cell lines exhibited no increase in radionuclide binding. The epigenetic upregulation of SSTR2 expression could improve the efficacy and toxicity profile for targeted radionuclide therapy of NETs with [177Lu]DOTATATE.

In vivo biodistribution studies demonstrated high tumor uptake and rapid renal clearance for [203Pb]PSC-PEG2-TOC. The administration of 4 fractionated doses of [ 212Pb]PSC-PEG2-TOC produced 100% complete tumor responses at 100 days post therapy initiation and was well-tolerated compared to [177Lu]DOTATATE, which produced improved PFS (28.5 days), but no complete responses.CONCLUSIONS These data demonstrate that [203/212Pb]PSC-PEG2-TOC has the potential to produce a higher rate of objective tumor responses than beta-particle emitting therapeutics for NETs.

There are limited treatment options with current standard therapies for well-differentiated aggressive grade 2 and grade 3 (Ki-67 index 15−55%) GEP-NETs; however, these may include somatostatin analogues; peptide receptor radionuclide therapy (PRRT); molecular targeted therapies (everolimus or sunitinib); chemotherapy; and cytoreductive procedures...More sites and countries will follow. CONCLUSIONS COMPOSE results are expected to inform about optimal treatment options for patients with well‑differentiated aggressive grade 2 and grade 3 SSTR+ GEP-NETs, including for first-line therapy.

A higher radiosensitizing potential of PARPi was observed for EBRT compared to Lu-DOTATATE. Our data reinforce the need for dedicated RNT radiobiology studies, in order to derive its maximum therapeutic benefit.

Postoperatively, the patient received combined chemotherapy of 5-fluorouracil with interferon for six months and since has remained asymptomatic. The patient received somatostatin analogue therapy followed by long-acting release octreotide analogue therapy (30 mg/month) showing a partial improvement of relevant biomarkers. Two years later, carcinoid syndrome symptoms reappeared and due to the tumors expression of somatostatin receptors the patient received peptide receptor radionuclide therapy with 177Lu-DOTATATE that resulted in both clinical and biochemical improvements.

First-line PRRT with 177Lu-DOTATATE and combinations of this therapy with cytotoxic drugs are currently under investigation. New radiolabeled somatostatin receptor ligands include SSAs coupled with alpha radiation emitting radionuclides and somatostatin receptor antagonists coupled with radionuclides.

Radiolabeled somatostatin analogs are contributive for the management of recurrent MTC. 68Ga-DOTATAE PET-CT showed a relatively high detection rate in recurrent MTC. In addition, PRRT with 177Lu-DOTATATE was found to be a safe alternative therapeutic option for MTC.

P2, N=32, Recruiting, NYU Langone Health | Trial completion date: May 2023 --> May 2025 | Trial primary completion date: May 2022 --> May 2024

If the calculated TEDE meets the regulatory limits, the patient is eligible for release and provided instructions with radiation precautions. This study aims to determine a mean transmission factor to the patient to improve accuracy and individualize the estimation of the TEDE.

On the other hand, in order to operate the rooms, it is necessary to set up and decontaminate the rooms for each treatment, which requires specialized knowledge and manpower. Since there is a growing demand for radionuclide therapies, it is important to promote the appropriate introduction of this therapy and to establish a collaborative network for this purpose.

Furthermore, three and seven patients had grade II and grade I anemia, respectively. Conclusion  Since PRRT using Lu-DOTATATE has a favorable response rate and few adverse effects and improves the quality of life in NETs, it can be used as an effective therapeutic option, especially in nonoperative, metastatic, and progressive NETs.

P1, N=60, Recruiting, Peking Union Medical College Hospital | Unknown status --> Recruiting | N=20 --> 60 | Trial completion date: Dec 2019 --> May 2023 | Trial primary completion date: Dec 2019 --> Dec 2022

The aim of this study was to provide outcomes of patients harboring refractory meningiomas treated by 177Lu-DOTATATE and an overall analysis of progression-free survival at 6 months (PFS-6) of the same relevant studies in the literature. SSTR-targeted PRRT allowed us to achieve prolonged PFS-6 in patients with WHO grade I and II progressive refractory meningiomas, except the most aggressive WHO grade II tumors. Large scale randomized trials are warranted for the better integration of PRRT in the treatment of refractory meningioma into clinical practice guidelines.