P2, N=18, Recruiting, Weill Medical College of Cornell University | Trial completion date: Feb 2025 --> Sep 2026 | Trial primary completion date: Feb 2024 --> Sep 2026

P=N/A, N=89, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=50 --> 89

P1/2, N=39, Recruiting, Novartis Pharmaceuticals | Phase classification: P1 --> P1/2

P1/2, N=37, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

P2, N=93, Active, not recruiting, Jonsson Comprehensive Cancer Center | Recruiting --> Active, not recruiting

P2, N=15, Not yet recruiting, University of Washington | Initiation date: Apr 2024 --> Aug 2024

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

P3, N=446, Active, not recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Trial completion date: Dec 2025 --> Dec 2028

P1, N=49, Active, not recruiting, Oncoinvent AS | Recruiting --> Active, not recruiting

P1/2, N=67, Active, not recruiting, Oncoinvent AS | Recruiting --> Active, not recruiting

P1/2, N=100, Not yet recruiting, Advanced Imaging Projects, LLC | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2024 --> Aug 2025

In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering β-emitting 177Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2)...However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose.

This study confirms that the estimated bone marrow dose is significantly lower with the blood-based method than with the image-based method. The blood-based method with a bi-exponential model proved particularly useful, without the need for blood samples after 24h post-injection. Nevertheless, this blood-based method is based on an assumption that needs to be more validated. The important difference between the two methods does not allow to determine the optimal one to estimate the true absorbed dose and further studies are necessary to compare with biological effects.

The therapeutic efficacy of Pluvicto™ at low radioactive doses can be effectively enhanced by the combination with L19-IL2. Our findings warrant further clinical exploration of this novel combination modality.

P1/2, N=36, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1, N=118, Recruiting, Bayer | Not yet recruiting --> Recruiting

In this work, we present an updated appraisal of the literature, reviewing the recent advances in the use of established radiotheranostic agents such as radioiodine for differentiated thyroid carcinoma and Iodine-131-labeled meta-iodobenzylguanidine therapy of tumors of the sympathoadrenal axis as well as the recently approved 177Lu-DOTATATE and 177Lu-PSMA for differentiated neuroendocrine tumors and advanced prostate cancer, respectively. We also discuss the radiotheranostic agents that have been comprehensively characterized in preclinical studies and have shown some clinical evidence supporting their safety and efficacy, especially those targeting fibroblast activation protein (FAP) and chemokine receptor 4 (CXCR4) and those still being investigated in preclinical studies such as those targeting poly (ADP-ribose) polymerase (PARP) and epidermal growth factor receptor 2.

Clinical responders possessed lower circulating frequencies of Ki67+ T and myeloid cells at baseline and higher circulating frequencies of TIM-3+ T and myeloid cells by week 9. Although R223+P did not induce T-cell infiltration into the tumor microenvironment, exhaustion of induced peripheral T-cell immune responses may dampen the combination's clinical activity.

The use of metabolically stabilized, radiolabeled somatostatin (SST) analogs ([68Ga]Ga/[177Lu]Lu-DOTA-TATE/TOC/NOC) is well established in nuclear medicine...The involvement of neprilysin (NEP) in the metabolism of [111In]In-XG1 was confirmed by coadministration of Entresto®, a registered antihypertensive drug, in vivo releasing the selective and potent NEP-inhibitor sacubitrilat...To corroborate the imaging data, the tumors and the kidneys were excised and analyzed with a γ-counter. Even if receptor-specific tumor uptake for [111In]In-XG1 could be confirmed (1.61% IA/g), further optimization is required to improve its pharmacokinetic properties for radiotracer development.

P4, N=6, Recruiting, Vanderbilt-Ingram Cancer Center | Not yet recruiting --> Recruiting | Trial completion date: Mar 2026 --> Feb 2028 | Initiation date: Sep 2023 --> Apr 2024 | Trial primary completion date: Mar 2025 --> Feb 2027

PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

[177Lu]Lu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy.

P1, N=43, Active, not recruiting, Tufts Medical Center | Recruiting --> Active, not recruiting | N=25 --> 43 | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=62, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Aug 2025 --> Oct 2026 | Trial primary completion date: Apr 2024 --> Jan 2026

P2, N=135, Not yet recruiting, European Organisation for Research and Treatment of Cancer - EORTC

[177Lu]Lu-DPI-4452 demonstrated strong tumor growth inhibition in 2 xenograft mouse models. Thus, the 2 agents potentially provide a theranostic approach for selecting and treating patients with CAIX-expressing tumors such as ccRCC, CRC, and pancreatic ductal adenocarcinoma.

P2, N=136, Not yet recruiting, Mayo Clinic | Phase classification: P4 --> P2

P2, N=10, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

P1, N=25, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

This denies many patients with adequate somatostatin receptor expression and biochemical profiles from the beneficial effects of PRRT on the quality of life, daily function, and overall survival. The 2 cases highlight the favorable response of PRRT in patients with metastatic neuroendocrine tumor having a very poor performance status initially.

This initial study suggests that 225Ac-DOTATATE is a potentially promising option for treating NENs with elevated SSTR expression, with an acceptable toxicity profile and well-tolerated adverse effects.

P1, N=20, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

P1/2, N=30, Active, not recruiting, Peter MacCallum Cancer Centre, Australia | Recruiting --> Active, not recruiting

P1, N=10, Not yet recruiting, University of Wisconsin, Madison | Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025

P1, N=40, Recruiting, Chengdu New Radiomedicine Technology Co. LTD.

P=N/A, N=347, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P2, N=16, Active, not recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Mar 2023 --> Sep 2024

P3, N=450, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

The antitumor efficacy of [67Cu]Cu-EB-TATE is comparable to that of [177Lu]Lu-EB-TATE, with [67Cu]Cu-EB-TATE being slightly more effective than [177Lu]Lu-EB-TATE for complete remission of small tumors. [67Cu]Cu-EB-TATE therefore warrants clinical development.

As determined by receiver operating characteristic (ROC) curve analysis, tetanus-specific IL-10 spots at baseline had the highest predictive value (p = 0.005) for tumor burden at month 6, with an area under the curve (AUC) of 0.90 (sensitivity 100%, specificity 78%). In conclusion, we observed an additive effect of treatment with 223Ra on immune function and found that IL-10 secretion at baseline predicted tumor burden at month 6 after treatment.

P1, N=9, Recruiting, Molecular Targeting Technologies, Inc. | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=37, Not yet recruiting, Dana-Farber Cancer Institute