lutetium lu-177 tezuvotide tetraxetan (177Lu-rhPSMA-10.1) / Bracco, Blue Earth Therapeutics - LARVOL DELTA

NeoAdjuvant Theranostic Lutetium Study: The Nautilus Trial (clinicaltrials.gov) - P1/2 | N=6 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CTCs • FOLH1

Dosimetry analysis of a Phase 1 trial of 177Lu -rhPSMA-10.1 Following PSMA-PET–Guided Salvage Radiotherapy in Post-Prostatectomy Biochemical Recurrence (SNMMI 2026) - P1 | "The kidneys received the highest absorbed dose followed by salivary glands. In this early disease low malignancy burden population, renal and other organ dosimetry were slightly above those reported in Phase 1 data for 177Lu-rhPSMA-10.1 in mCRPC patients [1]. The observed higher organ doses may be explained by a lower disease burden in this cohort compared to the mCRPC population, where a "sink effect" from PSMA-avid lesions reduces organ exposure."

P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Prostate Cancer • Solid Tumor

Safety profile from a Phase 1 study of external beam salvage radiotherapy in biochemical recurrence post radical prostatectomy followed by upfront adjuvant 177Lu-rhPSMA-10.1. (SNMMI 2026) - "Post-prostatectomy salvage RT followed by upfront adjuvant 177Lu-rhPSMA-10.1 is feasible and well tolerated, without significant toxicity. The absence of grade ≥3 AEs and predominance of grade 1-2 AEs align with findings from Dierks et al. [5] on 177Lu-rhPSMA-10.1 safety in metastatic prostate cancer."

Clinical • P1 data • Constipation • Dental Disorders • Dry Eye Disease • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Leukopenia • Ophthalmology • Prostate Cancer • Solid Tumor • Xerostomia

Safety profile from a Phase 1 study of external beam salvage radiotherapy in biochemical recurrence post radical prostatectomy followed by upfront adjuvant 177Lu-rhPSMA-10.1. (SNMMI 2026) - "Post-prostatectomy salvage RT followed by upfront adjuvant 177Lu-rhPSMA-10.1 is feasible and well tolerated, without significant toxicity. The absence of grade ≥3 AEs and predominance of grade 1-2 AEs align with findings from Dierks et al. [5] on 177Lu-rhPSMA-10.1 safety in metastatic prostate cancer."

Clinical • P1 data • Constipation • Dental Disorders • Dry Eye Disease • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Leukopenia • Ophthalmology • Prostate Cancer • Solid Tumor • Xerostomia

Dosimetry analysis of a Phase 1 trial of 177Lu -rhPSMA-10.1 Following PSMA-PET–Guided Salvage Radiotherapy in Post-Prostatectomy Biochemical Recurrence (SNMMI 2026) - P1 | "The kidneys received the highest absorbed dose followed by salivary glands. In this early disease low malignancy burden population, renal and other organ dosimetry were slightly above those reported in Phase 1 data for 177Lu-rhPSMA-10.1 in mCRPC patients [1]. The observed higher organ doses may be explained by a lower disease burden in this cohort compared to the mCRPC population, where a "sink effect" from PSMA-avid lesions reduces organ exposure."

P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Prostate Cancer • Solid Tumor

Evaluation of a synergistic drug combination with 177Lu-rhPSMA-10.1 for prostate cancer: Results of an in vitro screen and in vivo proof of concept study (AACR 2024) - "Through an extensive in vitro screen, we identified Cobimetinib to have potential for a synergistic anti-tumor effect in combination with 177Lu-rhPSMA-10.1. This may be due to inhibition of the MEK-MAPK pathway by Cobimetinib during DNA damage response, resulting in radiosensitization of cancer cells to 177Lu-labeled RLT agents such as 177Lu-rhPSMA-10.1. This novel combination showed an enhanced therapeutic efficacy vs the single agents in 22Rv1 xenografts and the lack of overlapping monotherapy toxicity reported in the clinic supports clinical investigation in men with PCa."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

NeoAdjuvant Theranostic Lutetium Study: The Nautilus Trial (clinicaltrials.gov) - P1/2 | N=6 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | N=36 ➔ 6 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CTCs • FOLH1

First Patients in the UK Receive Doses of Blue Earth Therapeutics' Investigational Radiopharmaceutical Therapy Lutetium (177Lu) rhPSMA-10.1 Injection for Metastatic Castrate Resistant Prostate Cancer (PRNewswire) - "The patients received Lutetium (177Lu) rhPSMA-10.1 Injections at both St Bartholomew's Hospital, London, and The James Cook University Hospital, Middlesbrough."

Trial status • Castration-Resistant Prostate Cancer

NCI-2023-03480: Radioligand Therapy After PSMA PET Guided External Beam Radiotherapy for Treating Post-Prostatectomy Patients With Biochemically Recurrent Prostate Cancer (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Emory University | Recruiting ➔ Active, not recruiting | N=10 ➔ 6

Enrollment change • Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Tumour Dosimetry - It’s a Gray Area: Analysing the Importance of Lesion-Level Dosimetry Methods in 177 Lu-PSMA Targeted Therapy (EANM 2025) - "Figure 2 shows the estimated tumour specific absorbed dose coefficient in Gy/GBq by article referenced in the meta-analysis, alongside the results from the Phase I 177 Lu-rhPSMA-10.1 trial, BET-PSMA-121, with the method category...Without harmonisation of methods, the utility of dosimetry data, and the establishment of dose response relationships will remain confounded. Given the significant challenges establishing reliable tumour absorbed dose estimates given significant inter-patient biological variation, controlling for method is hugely important. At a minimum, studies employing dosimetry should clearly state their lesion selection and contouring methods to allow for more robust and unbiased comparisons."

Oncology • FOLH1

More Bang For Your Becquerel: A Novel Approach to “Dosing” in 177 Lu-PSMA Radioligand Therapy (EANM 2025) - "However, this approach must be carefully considered in the context of potential increased toxicity risks. As a result of this work, the Phase 2 component of this study will compare the efficacy and safety of this "font-loading" dosing strategy with a fixed per-cycle activity approach, where the interval between the first 3 cycles is shortened to 3 weeks, to explore PSMA RLT dose optimisation with 177 Lu-rhPSMA-10.1."

Castration-Resistant Prostate Cancer • Prostate Cancer

Investigating the Accuracy of Single-cycle Dosimetry with Novel PSMA-targeted Radioligand Therapy 177Lu-rhPSMA-10.1 (SNMMI 2025) - P1/2 | "Acceptable absorbed dose value estimates for key at-risk organs and tumors can be achieved using multi-timepoint imaging in Cycle 1 followed by a single 48-h timepoint at subsequent cycles. Despite the higher percentage errors for red marrow, the errors in absolute absorbed dose were reasonable. This approach to dosimetry offers an acceptable balance between imaging burden and data accuracy; these results support adopting a reduced dosimetry protocol for the estimation of cumulative doses over multiple cycles of treatment in the Phase 2 study."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Investigating the Accuracy of Single-cycle Dosimetry with Novel PSMA-targeted Radioligand Therapy 177Lu-rhPSMA-10.1 (SNMMI 2025) - P1/2 | "Acceptable absorbed dose value estimates for key at-risk organs and tumors can be achieved using multi-timepoint imaging in Cycle 1 followed by a single 48-h timepoint at subsequent cycles. Despite the higher percentage errors for red marrow, the errors in absolute absorbed dose were reasonable. This approach to dosimetry offers an acceptable balance between imaging burden and data accuracy; these results support adopting a reduced dosimetry protocol for the estimation of cumulative doses over multiple cycles of treatment in the Phase 2 study."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Organ and Tumor Dosimetry of a Novel PSMA-targeted Radioligand Therapy 177Lu-rhPSMA-10.1: Results from a Phase 1 Study (SNMMI 2025) - P1/2 | "177Lu-rhPSMA-10.1 delivers high radiation doses to tumors compared with normal organs, and this dataset suggests it has an improved therapeutic index compared with previously reported values for first generation PSMA-targeted RLT. Importantly, tumor selection and delineation methods have a significant impact on reported tumor doses and standardization of methods across trials should be targeted. The observed normal organ absorbed doses will allow administration of a high cumulative therapeutic activity."

P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Salivary Gland Cancer • Solid Tumor

Organ and tumour dosimetry of 177Lu-rhPSMA-10.1, a novel PSMA-targeted therapy: results from a Phase I trial. (PubMed, Eur J Nucl Med Mol Imaging) - "177Lu-rhPSMA-10.1 delivers high radiation doses to tumours vs. normal organs, facilitated by its favourable pharmacokinetics. Cumulative doses to normal organs were well within established tolerable limits, suggesting higher cumulative radioactivity could be administered in clinical trials. The observation of decreasing tumour absorbed dose with subsequent cycles also supports the exploration of front-loading radioactivity in Phase II."

Journal • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Salivary Gland Cancer • Solid Tumor

Blue Earth Therapeutics initiates Phase 2 Clinical Trial evaluating the efficacy and safety of Lutetium (177Lu) rhPSMA-10.1 Injection in metastatic castrate resistant prostate cancer (PRNewswire) - "Blue Earth Therapeutics today announced further progress in development of its radiohybrid, lutetium-labelled, PSMA targeted, investigational radioligand therapy, with enrolment of the first two patients in a Phase 2 clinical trial. The primary measure of efficacy in the study will be the proportion of patients achieving a ≥50% reduction in PSA levels, as well as assessing radiographic progression-free survival and patient safety (NCT05413850). The study is testing multiple dosing regimens that focus on delivering higher radiation doses when tumor burden is usually highest, at the beginning of treatment....1st study results could be available as soon as H1 2026."

P2 data • Trial status • Castration-Resistant Prostate Cancer

BET-PSMA-121: Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection (clinicaltrials.gov) - P1/2 | N=82 | Recruiting | Sponsor: Blue Earth Therapeutics Ltd | N=150 ➔ 82 | Trial completion date: Oct 2026 ➔ Mar 2028

Enrollment change • Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • Urology

Preclinical Evaluation of 177Lu-rhPSMA-10.1, a Radiopharmaceutical for Prostate Cancer: Biodistribution and Therapeutic Efficacy. (PubMed, J Nucl Med) - "Overall, compared with 177Lu-PSMA-I&T, 177Lu-rhPSMA-10.1 suppressed tumor growth for longer than 177Lu-PSMA-617 (inhibition from day 39 onward [P < 0.05] versus on day 49 only [P < 0.05]). In preclinical models, 177Lu-rhPSMA-10.1 shows a favorable tumor-to-kidney uptake ratio, and significant antitumor effects, indicating it to be a promising next-generation radiopharmaceutical therapy."

Journal • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Blue Earth Therapeutics Reports Key Results from Lutetium (177Lu) rhPSMA-10.1 Injection Phase 1 Clinical Trial (PRNewswire) - P1/2 | N=150 | NCT05413850 | Sponsor: Blue Earth Therapeutics Ltd | "Radiation dosimetry and pharmacokinetic data from the 13 metastatic castrate resistant prostate cancer patients enrolled in the Phase 1 portion of a Phase 1/2 clinical trial...showed proportionately higher absorbed radiation doses in tumours than in critical healthy tissues such as the kidneys. The data compares favourably to published data on first-generation PSMA-targeted radioligand therapies....The Phase 1 data shows that Lutetium (177Lu) rhPSMA-10.1 Injection has high ratios for absorbed radiation dose to tumours vs. dose to healthy tissues, with a measured mean tumour to salivary gland ratio of 73 and tumour to kidney ratio of 32. Median absorbed radiation dose to tumours defined by SPECT imaging was 8.9 Gy for each GBq of administered radioactivity.....Phase 2 trial design will seek to maximise radiation doses to tumor and extend the duration of therapy, with first...patients expected to enroll this quarter."

P1 data • Trial status • Castration-Resistant Prostate Cancer

NeoAdjuvant Theranostic Lutetium Study: The Nautilus Trial (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2026 ➔ Dec 2027 | Trial primary completion date: Jun 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CTCs • FOLH1

Blue Earth Therapeutics Ltd announces completion of $76.5M Series A financing to accelerate development of next generation targeted radioligand therapies (PRNewswire) - "Blue Earth Therapeutics Ltd...announced closing of a $76.5M Series A financing. The round was led by Soleus Capital and co-led by Sands Capital Management with existing investor Bracco Imaging SpA also participating. Woodline Partners and PBM Capital also joined in the financing as new institutional investors....Resources support Phase 2 studies for Lutetium (177Lu) rhPSMA-10.1 and Actinium (225Ac) rhPSMA-10.1, and development of differentiating data compared to 1st generation prostate cancer radioligand therapies."

Financing • Prostate Cancer

Blue Earth Therapeutics Advances Clinical Development of Lutetium (177Lu) rhPSMA-10.1 Injection with Promising Phase 1 Data (PRNewswire) - P1/2 | N=NA | "Blue Earth Therapeutics Ltd...announced further positive developments for its novel investigational radioligand therapies....Early data from the trial suggests an encouraging safety profile. Radiation dosimetry performed for up to three cycles showed delivery of high tumour absorbed radiation doses relative to the dose delivered to the key normal organs, such as kidney and salivary glands....This data opens the way for the Phase 2 portion of the Phase 1/2 trial to start later this year. The company has shared the intended Phase 2 study design with regulators and, subject to trial safety committee agreement, will test innovative dosing regimens in the Phase 2 study....'We remain on track for the opening of Phase 2 in the next few months. We also expect to see the full Phase 1 results presented at a scientific meeting in 2025'."

P1 data • Trial status • Prostate Cancer

Blue Earth Therapeutics Announces Promising Results from Preclinical Evaluation of Synergistic Drug Combinations with Radiopharmaceutical 177Lu-rhPSMA-10.1 for Treatment of Prostate Cancer (Businesswire) - "Blue Earth Therapeutics...announced results from a series of preclinical analyses designed to identify synergistic combinations of known anticancer drugs with ¹⁷⁷Lu-rhPSMA-10.1 radioligand therapy, and from a preclinical efficacy analysis of the lead novel drug combination for the treatment of prostate cancer. Results from a systematic in vitro screen identified MEK inhibitor cobimetinib as a lead candidate with potential for synergistic combination with ¹⁷⁷Lu-rhPSMA-10.1, and the preclinical efficacy analysis showed enhanced therapeutic effect of this drug combination when compared to the untreated control and to the single agents alone. The data were presented in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, Calif."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

NeoAdjuvant Theranostic Lutetium Study: The Nautilus Trial (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs • FOLH1

Blue Earth Therapeutics Announces Publication of Results from Independent Clinical Experience with 177Lu-rhPSMA-10.1 in Treatment of Metastatic Castrate Resistant Prostate Cancer (Businesswire) - "Blue Earth Therapeutics, a Bracco company...is pleased to share the publication of promising early clinical data with ¹⁷⁷Lu-rhPSMA-10.1 from independent clinical experience by physicians at the University Hospital Augsburg, Germany...In the 4 consecutive patients with metastatic prostate cancer who were evaluated, when looking at radiologic progression free survival (rPFS), 2 patients had not progressed at 24 and 18 months of follow-up...Starting prostate-specific antigen (PSA) levels were reduced by 100%, 99%, 88% and 35% for the 4 individual patients. There were no serious treatment-related adverse events....The Company’s investigational Phase 1/2 clinical trial (NCT05413850) evaluating the safety, tolerability, dosimetry and anti-tumor activity of ¹⁷⁷Lu-rhPSMA-10.1 in eligible men with metastatic castrate-resistant prostate cancer (mCRPC) is underway in the United States."

Retrospective data • Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer