BAY 3563254 / Bayer - LARVOL DELTA

First-in-human assessment of actinium-225-prostate-specific membrane antigen (225Ac-PSMA)-Trillium (BAY 3563254) in mCRPC: Dose-escalation results of the phase 1 PAnTHa study. (ASCO-GU 2026) - P1 | "225Ac-PSMA-Trillium was well-tolerated with no DLTs. PSA50 response rates were 83% at the RDE and 93% in all pts with SUVmean >10. These promising data support the further investigation of the molecule."

First-in-human • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Prostate Cancer • FOLH1

Comparative evaluation of 225Ac-PSMA-Trillium with other 225Ac-PSMA-SMOL assets in a preclinical prostate cancer xenograft model (AACR 2026) - P1 | "Here, we compared 225Ac-PSMA-Trillium with three other 225Ac-PSMA-SMOLs, i.e., 225Ac-PSMA-617, 225Ac-PSMA-R2 and 225Ac-PSMA-I&T, which all utilize a DOTA chelator for complexing 225Ac...177Lu-PSMA-617 SPECT imaging was performed to evaluate tumor uptake...In summary, 225Ac-PSMA-Trillium showed the highest tumor uptake and the strongest tumor growth inhibition with a clear dose response compared with the other 225Ac-PSMA-SMOLs. These data support the clinical development of 225Ac-PSMA-Trillium (NCT06217822)."

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

Bayer Reports Results for the Investigational Targeted Radionuclide Therapy 225Ac-PSMA-Trillium in Advanced Metastatic Prostate Cancer (Businesswire) - "Data from PAnTHa, the global Phase I first-in-human, dose-escalation study were presented during the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium....Data support advancing 225Ac-PSMA-Trillium to the next phase of development....The dose for expansion was successfully identified, with ≥80% of patients achieving a PSA50 response at the expansion dose."

First-in-human • P1 data • Castration-Resistant Prostate Cancer

PAnTHA: First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P1 | N=235 | Recruiting | Sponsor: Bayer | N=135 ➔ 235

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

Biodistribution and contribution of in vivo generated daughter radionuclides to the antitumour efficacy of 225Ac-PSMA-Trillium (EANM 2024) - "225Ac-PSMA-Trillium demonstrates a relatively slow pharmacokinetics profile and marked tumour uptake, which is consistent with its albumin-binding properties. Bismuth-213 and francium-221, the alpha-emitting daughter radionuclides of actinium-225, are predominantly retained in the tumour. Daughter radionuclides generated in the blood were more readily redistributed to the kidneys, salivary glands, or other organs."

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

Bayer Starts Phase I Study With Novel Targeted Radionuclide Therapy 225Ac-PSMA-Trillium in Advanced Metastatic Prostate Cancer (Businesswire) - "Bayer announced today initiation of dosing in a Phase I first-in-human clinical study with ²²⁵Ac-PSMA-Trillium (BAY 3563254), a next-generation targeted alpha therapy. The investigational candidate, labeled with actinium-225 and comprising a novel PSMA (prostate-specific membrane antigen) -targeting small molecule with a customized albumin-binding moiety, is designed to potentially improve therapeutic efficacy and reduce side effects in normal organs such as salivary glands. The dose-escalation study (NCT06217822) will evaluate the safety, tolerability and efficacy of ²²⁵Ac-PSMA-Trillium in patients with advanced metastatic castration resistant prostate cancer (mCRPC)."

Trial status • Metastatic Castration-Resistant Prostate Cancer

Actinium-225 -PSMA-Trillium (BAY 3563254): Preclinical evaluation and clinical imaging study of a novel 225Ac-labeled PSMA-targeting small molecule triad for the treatment of mCRPC (AACR 2024) - P1 | "Importantly, 111In-PSMA-Trillium showed robust uptake and prolonged retention in tumors, and reduced uptake and relatively fast washout from salivary glands. Based on these preclinical data and clinical imaging results, a therapeutic first-in-human trial to evaluate 225Ac-PSMA-Trillium in patients with prostate cancer is anticipated to begin enrolling patients in the first half of 2024."

Preclinical • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Preclinical evaluation of an actinium-225 labeled PSMA-targeting small molecule (225Ac-PSMA-Trillium (BAY 3563254)) for the treatment of metastatic castration resistant prostate cancer (mCRPC) (AACR 2024) - P1 | "In the androgen independent PDX KuCaP-1 model, a single dose of 250 kBq/kg 225Ac-PSMA-Trillium induced strong tumor growth inhibition over the course of 35 days. A first-in-human trial with 225Ac-PSMA-Trillium is anticipated to start in the first half of 2024."

Metastases • Preclinical • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

Bayer and Vividion Therapeutics to highlight advancing oncology portfolio at AACR 2024 Annual Meeting (Bayer Press Release) - "Bayer and Vividion Therapeutics, Inc. (Vividion) will present the latest research on their advancing oncology portfolio at the upcoming American Association for Cancer Research (AACR) 2024 Annual Meeting....During the New Drugs on the Horizon session Bayer will introduce actinium-225 (225Ac)-PSMA-Trillium....The data presented will include preclinical in vitro and in vivo characterization....Another abstract will highlight the synergistic anti-cancer effects of targeted alpha therapy radium-223 dichloride (Xofigo) in combination with darolutamide in preclinical prostate cancer models....Vividion will present its latest research on the development and characterization of novel preclinical covalent inhibitors of the RAS-PIK3CA interaction, preventing RAS mediated activation of PIK3CA."

Preclinical • Metastatic Castration-Resistant Prostate Cancer

PAnTHA: First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P1 | N=118 | Recruiting | Sponsor: Bayer | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

PAnTHA: First-in-human Study of 225Ac-PSMA-Trillium (BAY 3563254) in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P1 | N=118 | Not yet recruiting | Sponsor: Bayer

Metastases • New P1 trial • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor