Citations

4173 Background: [ 212 Pb]VMT-α-NET is an alpha-particle radiation-delivering agent targeted to somatostatin receptor type 2 (SSTR2)-expressing tumors. Here, we present safety and efficacy results from the dose-finding phase 1/2a clinical trial (NCT05636618). Methods: This phase 1/2a dose-escalation study uses a Bayesian algorithm to identify an optimal dose of [ 212 Pb]VMT-α-NET for participants with advanced, well-differentiated NETs expressing SSTR2. Eligible participants must have unresectable or metastatic disease, documented radiologic progression following at least one prior systemic treatment, and evidence of SSTR2 expression (Krenning Score ³2) in ≥1 lesion confirmed on an FDA-approved somatostatin receptor PET scan. Patients previously treated with systemic peptide receptor radionuclide therapy (PRRT) are excluded from enrollment. During the dose-finding phase, participants may receive up to four administrations of [ 212 Pb]VMT-α-NET at their assigned dose level, and they are monitored for dose-limiting toxicities (DLTs) for 42 days and safety throughout the study. Efficacy is evaluated by investigators according to RECIST criteria v1.1. Dosimetry is included as a supportive analysis. Results: As of the 10-Dec-2025 data cut-off (DCO), 56 participants had been enrolled across Cohorts 1, 2, and 3 and received at least one dose of [ 212 Pb]VMT-α-NET: 2 participants in Cohort 1 (2.5 mCi), 46 in Cohort 2 (5 mCi), and 8 in Cohort 3 (6 mCi). No dose-limiting toxicities, grade 5 adverse events, treatment-related discontinuations, serious renal events, dysphagia, or clinically meaningful treatment-related myelosuppression were observed. The median follow-up for all treated participants was 40 weeks (range 6–97). Efficacy has been summarized in this abstract for 25 participants (2 in Cohort 1 and 23 in Cohort 2). Nineteen of these 25 participants remained progression-free at the time of the DCO, with a median efficacy follow-up of 49 weeks (range 6–97). In Cohort 2, investigators observed RECIST v1.1 objective responses in 9 of 23 participants (39%), including 8 confirmed responses. Both participants in Cohort 1 continued to exhibit stable disease after two years of follow-up. Updated safety for all participants and updated efficacy for participants with sufficient maturity beyond the 25 summarized here will be presented at the congress. Conclusions: Treatment with [ 212 Pb]VMT-α-NET continues to demonstrate a favorable safety profile across all treated participants (n = 56) and shows signs of sustained efficacy at the 2.5 mCi and 5 mCi dose levels. The therapy has been well-tolerated with no observed dose-limiting toxicities or serious treatment-related adverse outcomes. Based on these encouraging safety and efficacy findings, the study is ongoing, and enrollment into Cohort 3 (6 mCi) remains active. Clinical trial information: NCT05636618 .

Abstract Background: [212Pb]VMT-a-NET is a novel, next generation alpha therapy agent for advanced somatostatin receptor 2 positive (SSTR2+) neuroendocrine tumors (NETs). Here, we present safety and efficacy update from the dose-finding phase 1/2a clinical trial (NCT05636618). Methods: Adults with well-differentiated unresectable or metastatic NETs, who were peptide receptor radionuclide therapy-naïve, showed progressive disease after at least one prior line of systemic therapy and demonstrated SSTR2-expression on PET images were treated with up to four cycles of study therapy at the assigned dose level. Participants were followed for dose-limiting toxicity (DLT) observation up to 42 days after the first dose. Efficacy was evaluated by investigators according to RECIST criteria v1.1. Results: As of 10-Dec-2025 (data cut-off [DCO]) a total of 56 participants were enrolled into Cohorts 1, 2 and 3, and received at least 1 dose of [212Pb]VMT-a-NET (n=2 in Cohort 1, n=46 in Cohort 2, and n=8 in Cohort 3 at a dose level of 2.5 mCi, 5 mCi, and 6 mCi, respectively). For data analysis purposes, participants were categorized into two different groups: a safety group and an efficacy group. The safety group included all participants treated by the DCO (n=56), while the efficacy group included only the Cohort 1 participants (n=2) and the first half of participants treated in Cohort 2 (n=23). Among all participants treated with at least 1 dose of [212Pb]VMT-a-NET (n=56), no DLTs, no grade 5 adverse events (AEs), no treatment-related discontinuations, no serious renal complications, no dysphagia and no clinically significant treatment-related myelosuppression were observed. Median follow-up time for all patients treated was 40 weeks (range: 6-97). Among the 25 participants followed for efficacy (n=2 in Cohort 1 and n=23 in Cohort 2), 19 out of 25 were with no progression as of the DCO. Median follow-up time for participants included in the efficacy group was 49 weeks (range: 6-97). Investigator-assessed RECIST v1.1 objective responses were observed in 9 out of 23 participants (39%) enrolled in the first half of Cohort 2 (8 confirmed). The 2 patients enrolled in Cohort 1 at 2.5 mCi still have stable disease after 2 years of follow up. Updated safety outcomes for all participants along with updated efficacy findings for participants in Cohorts 1 and 2 with sufficient maturity will be presented during the congress. Conclusions: Treatment with [212Pb]VMT-α-NET continues to be well-tolerated among all patients treated (n=56), and to show promising efficacy at the dose levels of 2.5 mCi and 5 mCi. The study is ongoing with Cohort 3 (6 mCi) currently open for enrollment. Citation Format: Thorvardur R. Halfdanarson, Richard L. Wahl, Vineeth Sukrithan, Brandon R. Mancini, Seyed A. Mosallaie, Savitha Balaraman, Gregory S. Sibley, Jason Starr, Lowell B. Anthony, Chih Y. Liao, Samuel H. Mehr, Jared Weiss, Robert A. Ramirez, Lucia Baratto, Wenjing Yang, Alaa Hanna, Stephen M. Keefe, Markus Puhlmann, Vikas Prasad. [212Pb]VMT-a-NET in advanced SSTR2+ neuroendocrine tumors: safety and preliminary efficacy results from dose-finding cohorts 1,2 and 3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT088.

Abstract Hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant vasculopathy affecting 1 in 5000 individuals, is the second most common inherited bleeding disorder worldwide. Despite this prevalence, comprehensive data on disease manifestations and complications remain limited. To address this gap, the US Congress allocated funding leading to the Comprehensive HHT Outcomes Registry of the United States (CHORUS), a prospective, 15-center longitudinal registry enrolling unselected patients with confirmed HHT. In this initial report, we describe findings from the first 600 participants, with a median age of 53 (range, 0-88) years and 60% female. Despite most participants developing typical HHT manifestations by age 13 years, the majority (63%) were not diagnosed until mid-to-late adulthood. Recurrent spontaneous epistaxis occurred in 95% of participants, chronic gastrointestinal bleeding in 30%, and heavy menstrual bleeding in 35% of postmenarche females, together resulting in moderate-to-severe mucosal bleeding in 76%. Iron deficiency and/or anemia were diagnosed in 68%, with 41% requiring IV iron and 25% requiring red cell transfusions. Serious complications of solid-organ arteriovenous malformations were frequent, including intracranial hemorrhage (3%), pulmonary hemorrhage (2%), venous thromboembolism (7%), arterial thromboembolism (11%), heart failure (7%), and pulmonary hypertension (7%). These data from CHORUS, the first national US registry of its kind, provide reliable, real-world estimates of the incidence, prevalence, and severity of numerous HHT manifestations and complications. HHT has a high burden of moderate-to-severe bleeding, anemia, thrombosis, and major neurologic and cardiopulmonary complications. There is a mean interval between first symptoms and diagnosis of >2 decades, during which substantial, serious, and preventable HHT morbidity, including early intracranial hemorrhage, may occur. This trial was registered at clinicaltrials.gov as NCT06259292.

TPS646 Background: SSTR-targeted RPT has transformed the treatment landscape for NETs, significantly improving clinical outcomes in phase 3 studies versus other targeted therapies. Nevertheless, disease progression and renal toxicity after treatment highlight the need for further improvement. Use of the α-emitter 225 Ac as the radioactive component has shown promising results in clinical studies: initial data from ACTION-1 suggest promising efficacy for RYZ101, a first-in-class, highly potent α-emitting RPT, in patients with SSTR+ GEP-NETs progressing after 2–4 cycles of 177 Lu-somatostatin analogs. RYZ401 is a cyclic 6-amino acid SSTR-targeting peptide agonist conjugated to a DOTA chelator bound to 225 Ac. Preclinical data have shown an improved therapeutic window versus DOTATATE. RYZ401 has the potential to deliver higher radiation doses to tumors, with improved renal clearance and lower kidney absorbed dose, potentially eliminating the need for amino acid infusion. Methods: RYZ401-101 is a global, multicenter, phase 1, first-in-human, dose-escalation/-expansion study designed to determine the recommended phase 2 dose (RP2D) and optimal treatment regimen, safety and tolerability, and preliminary efficacy of RYZ401 in patients with NETs and other selected solid tumors expressing SSTRs. Key eligibility criteria: histologically confirmed metastatic or unresectable well-differentiated NETs; WHO grade 1–3 (Ki-67 ≤55%); ≥1 SSTR PET-positive measurable lesion; and disease progression after ≥1 prior treatment line. In dose escalation, 6–18 patients will receive escalating doses of RYZ401 (2.0–11.1 MBq IV Q6W × 2–4 cycles); no amino acid co-infusion is planned. In dose expansion, approximately 80 patients will receive RYZ401 at the RP2D, 40 patients with well-differentiated GEP-NETs (cohort A) and 40 with other SSTR+ tumors including non-GEP-NETs (cohort B). Primary endpoints: dose-limiting toxicities in weeks 1–4 of treatment (dose escalation) and safety (dose expansion). Secondary endpoints: safety, pharmacokinetics, and efficacy outcomes (dose escalation and expansion). RYZ401 dosimetry will be evaluated in a sub-study of 10−16 patients. Enrollment is ongoing in the USA. Clinical trial information: NCT07165132 .

635 Background: [ 212 Pb]VMT-a-NET is an alpha therapy agent targeting somatostatin receptor subtype 2 (SSTR2)-expressing tumors. Here, we report the results of a prospective, open-label, Phase I/IIa trial (NCT05636618), assessing safety, tolerability, pharmacokinetics, and preliminary efficacy of [ 212 Pb]VMT-a-NET in patients with advanced neuroendocrine tumors (NETs). Methods: Adults with well-differentiated unresectable or metastatic SSTR2-expressing NETs, who are peptide receptor radionuclide therapy (PRRT) naïve, and who progressed on at least one prior line of systemic therapy, are eligible. Participants can receive up to four cycles of [ 212 Pb]VMT-a-NET at the assigned dose level. Participants are followed for dose-limiting toxicity (DLT) observation up to 42 days after the first dose. Efficacy is evaluated by investigators according to RECIST criteria v1.1. Results: As of 16-Aug-2025 (data cut-off [DCO]) a total of 48 participants were enrolled into cohorts 1 and 2 and received at least one dose of [ 212 Pb]VMT-a-NET (n=2 in Cohort 1, and n=46 in Cohort 2 at a dose level of 92.5 MBq and 185 MBq, respectively). Among all participants treated with at least one dose of [ 212 Pb]VMT-a-NET (n=48), no DLTs, no grade 4 or 5 adverse events (AEs), and no treatment-related discontinuations, were observed. Median follow-up time was 28 weeks (range: 6-93). Nine participants were followed for DLT observation (n=2 in cohort 1 and n=7 in cohort 2).Seven of these patients were with no progression as of the DCO. Three out of the seven participants enrolled at the dose level of 185 MBq achieved a confirmed partial response (PR). Median follow-up time for participants included in the efficacy group was 72 weeks (range: 6-93). Cohort 3, at a dose level of 222 MBq, has recently been opened for enrollment. At the DCO, 4 participants were enrolled in this cohort. Updated safety outcome for all participants along with updated efficacy findings for participants in Cohort 1 and 2 with sufficient maturity, will be presented during the congress. Conclusions: [ 212 Pb]VMT-a-NET showed a favorable safety profile and promising clinical benefit for patients with advanced SSTR2-expressing NETs treated at the dose levels of 92.5 MBq and 185 MBq. The study is ongoing with Cohort 3 (222 MBq) currently open for enrollment. Clinical trial information: NCT05636618 .

Abstract Hereditary hemorrhagic telangiectasia (HHT) causes severe recurrent epistaxis, chronic gastrointestinal bleeding, solid organ arteriovenous malformations, and significant anemia. Although it is the second most common inherited bleeding disorder worldwide, no approved therapies exist. The multicenter, US randomized, controlled PATH-HHT trial demonstrated efficacy of short-term pomalidomide treatment of epistaxis in HHT. However, questions regarding long-term safety, effectiveness, and utility for HHT-associated gastrointestinal bleeding remain. The PATH-HHT ATLAS (after trial longitudinal assessment study) was a multicenter US longitudinal observational study evaluating patients enrolled in PATH-HHT who continued pomalidomide after PATH-HHT through a poststudy drug access program, with ongoing close monitoring per PATH-HHT protocol and as mandated by the US Food and Drug Administration. Sixty-two patients treated with pomalidomide for HHT for up to 4.4 years were included. Significant, durable improvements in mean epistaxis severity score (5.55 points [baseline] to 2.80 points [month 12]; P< .0001) and mean hematologic support score (9.11 red cell unit equivalents [RUEs] during 6 months pretreatment to 5.73 RUEs [months 7-12]; P = .0056) were observed. Pomalidomide was less effective for gastrointestinal bleeding than for epistaxis, particularly in patients with high red blood cell transfusion requirements. Thirty-one patients (50%) underwent dose reduction from 4 mg daily, primarily due to neutropenia, but most maintained effectiveness at 2 or 3 mg daily. Over 105.2 patient-years of pomalidomide treatment, 0 patients developed peripheral neuropathy, 1 developed venous thromboembolism, and 5 developed serious infections. In conclusion, pomalidomide was effective for HHT-associated epistaxis over extended durations, albeit with nontrivial potential toxicities, and may be considered for certain patients with HHT. This trial was registered at www.clinicaltrials.gov as NCT07018401.

Abstract Background: [212Pb]VMT-a-NET is an alpha therapy agent targeting somatostatin receptor subtype 2 (SSTR2)-expressing tumors. Neuroendocrine tumors (NETs) generally express SSTR2 on their cell surface. Here, we report the results of a prospective, open-label, Phase I/IIa clinical trial evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of [212Pb]VMT-a-NET [NCT05636618]. Methods: The study design follows a Bayesian dose-finding algorithm. Main inclusion criteria include histologically proven well-differentiated unresectable or metastatic NETs, radiological evidence of progression on at least one prior line of systemic therapy, demonstration of lesional SSTR2 expression on an FDA-approved SSTR PET. Main exclusion criteria include: prior treatment with systemic PRRT-based therapies. In the dose finding phase, participants can receive up to four cycles of [212Pb]VMT-a-NET at the assigned dose level. Participants are followed for dose-limiting toxicity (DLT) observation up to 42 days after the first cycle. Efficacy is evaluated by investigators according to RECIST criteria v1.1. Here we report safety and preliminary efficacy data of participants enrolled in cohorts 1 and 2 at 92.5 MBq [2.5 mCi] and 185 MBq [5 mCi], respectively. Results: As of 30-Apr-2025 (data cut-off – DCO), a total of 42 participants were enrolled into the study. Nine of them were followed for DLT observation; thirty-three (33) additional participants were subsequently enrolled into cohort 2 to further evaluate safety and efficacy at the selected dose. For data analysis purposes, participants were divided into two different groups: a safety group and an efficacy group. The safety group included all participants enrolled by the DCO (n=42), while the efficacy group included only nine participants enrolled in cohort 1 (n=2) and cohort 2 (n=7) for DLT observation. Median follow up time for participants included in the safety group was 14 weeks (range:0,77); median follow up time for participants included in the efficacy group was 56 weeks (range: 6,77). In the safety group (n=42) we did not observe any DLTs, any grade 4 or 5 adverse events (AEs), any treatment-related discontinuations, any serious renal complications or myelosuppression, or any dysphagia. In the efficacy group (n=9) seven out of nine participants were with no progression as of the DCO, and four out of the seven participants enrolled in cohort 2 achieved a partial response (PR). Three PRs were confirmed, while one was pending confirmation at the time of DCO. Cohort 3, at a dose level of 222 MBq [6 mCi], has recently been opened for enrollment. Safety data for all treated participants and efficacy results for a mature subset will be presented at the congress. Conclusions: [212Pb]VMT-a-NET showed a favorable safety profile and promising clinical benefit for patients with advanced SSTR2-expressing NETs treated at the dose level of 185 MBq (5 mCi). The study is ongoing with cohort 3 currently open for enrollment. Citation Format: Vikas Prasad, Richard Wahl, Lilja Solnes, Savitha Balaraman, Gregory Sibley, Lowell Anthony, Brandon Mancini, Jason Starr, Vineeth Sukrithan, Chih-Yi Liao, Samuel Mehr, Lucia Baratto, Wenjing Yang, Alaa Hanna, Stephen Keefe, Markus Puhlmann, Thorvadur Halfdanarson. [212Pb]VMT-a-NET for somatostatin receptor subtype 2 (SSTR2)-expressing tumors: safety and preliminary efficacy results in patients with advanced neuroendocrine tumors (NETs) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C095 .

TPS5125 Background: Prostate cancer (PC) is common and despite recent advances in treatment options, patients with metastatic disease still have poor outcomes. The double PSMA binding moiety of SAR-bisPSMA in 64 Cu-SAR-bisPSMA (imaging) and 67 Cu-SAR-bisPSMA (therapy) may offer advantages compared to currently used single-target PSMA agents. Clinical evidence demonstrated 2-3 times higher uptake of 64 Cu-SAR-bisPSMA compared to the single-target PSMA agent, 68 Ga-PSMA-11. Pre-clinical efficacy data of 67 Cu-SAR-bisPSMA in mice showed statistically significant tumor growth inhibition and increased survival in a PC xenograft study. These results led to the development of the SECuRE trial, which aims to assess the safety and anti-tumor efficacy of 67 Cu-SAR-bisPSMA in patients with metastatic castrate resistant PC (mCRPC). Methods: SECuRE is a Phase I/IIa multi-center, open-label, non-randomized, dose-escalation and cohort expansion study of 64 Cu-SAR-bisPSMA and 67 Cu-SAR-bisPSMA in patients with mCRPC. The target population is patients who have progressed despite having at least one androgen receptor pathway inhibitor and demonstrate positivity on 64 Cu-SAR-bisPSMA PET. The study comprises 3 phases: Dosimetry (N=6), Dose Escalation (N~24) and Cohort Expansion (N=24). The 67 Cu-SAR-bisPSMA dose levels investigated in the Dose Escalation Phase are: 4 GBq (cohort 1, single dose), 8 GBq (cohort 2, single dose), 12 GBq (cohort 3, single dose) and 24 GBq across two doses (cohort 4, two doses at the maximum tolerated dose or maximum feasible dose [MTD/MFD] established in cohorts 1-3; two additional doses may be offered in case of radiological non-progression). In the Cohort Expansion phase, participants will receive 2 doses of 67 Cu-SAR-bisPSMA at the recommended dose determined in the Dose Escalation Phase (those with radiological non-progression may be offered up to 2 additional doses). A recent protocol amendment increased the number of participants from 14 to 24 in the Cohort Expansion phase, in which 8 will receive combination therapy of 67 Cu-SAR-bisPSMA with enzalutamide. The primary and key secondary objectives include assessment of 64 Cu- and 67 Cu-SAR-bisPSMA’s safety and dosimetry and determining the anti-tumor efficacy of 67 Cu-SAR-bisPSMA. Response to 67 Cu-SAR-bisPSMA will be assessed biochemically (≥50% decline in prostate-specific antigen) and radiographically (by RECIST V1.1 and PCWG3). Clinical trial information: NCT04868604 .

3005 Background: [ 212 Pb]VMT-α-NET, a next generation 212 Pb-based, SSTR2-targeted alpha-particle radiopharmaceutical therapy (RPT), was designed to achieve superior biodistribution via optimized tumor uptake and retention and rapid renal clearance. Results reported here are from the Phase 1/2a first-in-human study [NCT05636618]. Methods: Safety, pharmacokinetics, dosimetry and efficacy using RECIST v1.1 were investigated in the treatment of participants with [ 212 Pb]VMT-α-NET who had SSTR2-expressing, well-differentiated adult NETs of any grade. Participants received ≥1 prior therapy. No prior peptide receptor radionuclide therapy was allowed. The trial has multiple dose cohorts including 92.5 MBq (2.5 mCi, cohort 1) and 185 MBq (5 mCi, cohort 2) of administered activity based on a Bayesian modified toxicity probability interval (mTPI-2) design. Up to 8 participants per cohort were treated with 4 doses of [ 212 Pb]VMT-α-NET for DLT observation. Cohort 2 enrollment was expanded to further define the safety and efficacy profile at this dose level. Results: Nine (9) gastroenteropancreatic NET participants were enrolled into cohorts 1 and 2 for DLT observation. The ninth of these participants was enrolled more than 1 year prior to presentation of these data. Among these participants at the time of abstract submission, no DLTs were observed, and there were no grade 4, 5 or serious adverse events (SAEs). Specifically, no renal insufficiency or dysphagia were observed. Hematologic AEs were low grade and few in number. No treatment discontinuations due to AE occurred. Three (3) of the 7 cohort 2 participants enrolled for DLT observation achieved investigator-assessed partial responses (PRs). Two PRs were unconfirmed at the time of abstract submission. Durable progression-free survival (PFS) was consistently observed. More than 15 additional participants were enrolled in the cohort 2 expansion. Preliminary data for these patients will be reported at the congress. Conclusions: [ 212 Pb]VMT-α-NET is a well-tolerated, next generation RPT showing signs of clinical activity at early dose-levels in this phase 1/2a study. Based on these clinical data, further dose-escalation and development of this promising therapy are warranted. Clinical trial information: NCT05636618 .

Background More than 1 in 5 US adults live with mental illness. Novel therapies as complements to standard therapies are needed to improve patient well-being. Reiki is a biofield therapy that may improve well-being in mental health. Objective The primary aim of this study was to evaluate the feasibility of providing Reiki at a behavioral health clinic serving a low-income population. The secondary aim was to evaluate outcomes in terms of patients’ symptoms, emotions, and feelings before and after Reiki. Methods This was a mixed-methods, feasibility pilot study with a pre-post experimental design. Reiki was offered to adult outpatients at a community behavioral health center in Rochester, Minnesota. Patients with a stable mental health diagnosis seen between July 22, 2021, and May 18, 2023, completed surveys before and after the Reiki intervention and provided qualitative feedback. Patients were asked to report their ratings of pain, anxiety, fatigue, and feelings (eg, happy, calm) on 0- to 10-point numeric rating scales. Data were analyzed with Wilcoxon signed rank tests. Results Among 91 patients who completed a Reiki session during the study period, 74 (81%) were women. Major depressive disorder (71%), posttraumatic stress disorder (47%), and generalized anxiety disorder (43%) were the most common diagnoses. The study was feasible in terms of recruitment, retention, data quality, acceptability, and fidelity of the intervention. Patient ratings of pain, fatigue, anxiety, stress, sadness, and agitation were significantly lower, and ratings of happiness, energy levels, relaxation, and calmness were significantly higher after a single Reiki session. Conclusion The results of this study suggest that Reiki is feasible and could be fit into the flow of clinical care in an outpatient behavioral health clinic. It improved positive emotions and feelings and decreased negative measures. Implementing Reiki in clinical practice should be further explored to improve mental health and well-being.