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Evaluating the safety and effectiveness of a new treatment for advanced prostate cancer

A Phase 1 Open-label, First-in-human, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Actinium-225-macropa-pelgifatamab (BAY 3546828) in Participants With Advanced Metastatic Castration Resistant Prostate Cancer (mCRPC)

Phase 1 Interventional Bayer · NCT06052306

This study is testing a new treatment for advanced prostate cancer to see if it can help patients who have run out of other options.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment232 (estimated)
Ages18 Years and up
SexMale
SponsorBayer Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy, pelgifatamab, radiation
Locations30 sites (Duarte, California and 29 other locations)
Trial IDNCT06052306 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and anticancer activity of actinium-225-macropa-pelgifatamab (BAY3546828) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). The treatment targets prostate-specific membrane antigen (PSMA) on cancer cells and is designed for patients who have limited treatment options after previous therapies. Participants will be monitored for how the drug affects their bodies and its movement through the body. The study aims to provide insights into a potentially new therapeutic approach for a challenging cancer type.

Who should consider this trial

Good fit: Ideal candidates include men with advanced metastatic castration-resistant prostate cancer who have previously received at least one novel androgen axis drug and have limited treatment options.

Not a fit: Patients with early-stage prostate cancer or those who have not received prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new option for patients with advanced prostate cancer who have exhausted other therapies.

How similar studies have performed: While this approach is novel, similar studies targeting PSMA have shown promise in treating advanced prostate cancer.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* mCRPC with pathological confirmation of adenocarcinoma without small-cell or neuroendocrine features.
* Previous treatment with at least 1 Novel androgen axis drug (NAAD) (e.g., enzalutamide, apalutamide, darolutamide and/or abiraterone).
* Prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L).
* Prior taxane treatment:

  * Dose Escalation: Participants must either have had prior treatment with at least 1 but no more than 2 taxane regimens, or been deemed ineligible for or refused taxane therapy on consultation with their physician
  * Dose Expansion Group A: Participants must have had prior treatment with at least 1 but no more than 2 taxane regimens, in the castration-resistant setting
  * Dose Expansion Group B: Participants must not have received taxane therapy since becoming castration-resistant
  * Dose Expansion Group C: Participants must either have had prior treatment with at least 1 but no more than 2 taxane regimens\*, or been deemed ineligible for or refused taxane therapy on consultation with their physician \*A taxane regimen consists of a minimum of 2 treatment cycles (maximum number of cycles as per local guidelines). A treatment break within a taxane regimen may be given provided that another anticancer therapy is not administered during that time
* Prior treatment with an established 177Lu-PSMA therapy (i.e., dose activity and cycles comparable to approved treatments) is required for participants in Dose Expansion Group C only. More specifically, to qualify for this expansion group, participants must meet all of the following criteria:

  * Received a minimum of two cycles of 177Lu-PSMA
  * Not discontinued 177Lu-PSMA treatment due to intolerance; and
  * Not achieved a partial or complete response during the course of 177Lu-PSMA treatment.
* Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
* Adequate bone marrow, hepatic, and renal function, as assessed by the following laboratory requirements within 30 days before start of study intervention:

  * Hemoglobin ≥9.0 g/dL
  * Absolute neutrophil count (ANC) ≥1500/mm\^3
  * Platelet count ≥100,000/mm\^3
  * Total bilirubin ≤1.5 x the Upper limit of normal (ULN), or \<= 3 ULN if the participant has a confirmed history of Gilbert's syndrome (note that participants with Gilbert's syndrome should be carefully evaluated for other liver-related disorders that may impact their suitability for this study).
  * Alanine transaminase (ALT) and Aspartate transaminase (AST) ˂2.5 x ULN (≤5 x ULN for participants with liver involvement)
  * Participants on a stable dose of anticoagulation therapy are allowed to participate if they have no sign of bleeding or clotting, and Prothrombin time international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) test results are acceptable at the Investigator's discretion
  * Estimated glomerular filtration rate (eGFR) \>60 mL/min/1.73 m\^2, according to the Modified Diet in Renal Disease (MDRD) abbreviated formula and creatinine clearance (CrCl) \>60 mL/min based on Cockcroft-Gault formula
* Participants must have at least one Prostate-specific membrane antigen (PSMA)-positive distant metastatic lesion on the screening PSMA PET/CT scan using the study-designated PSMA PET tracers, as determined by the site Investigator. For eligibility purposes, a PSMA-positive lesion must have activity greater than the liver by visual assessment of the screening PSMA PET/CT. A PSMA-positive metastatic lesion should not correspond to a normal tissue structure or benign lesion.
* Documented progressive mCRPC per PCWG3, defined as meeting at least one of the following criteria:

  * PSA-progression (defined as 2 consecutive increases over a previous reference value obtained at a minimum of 1-week intervals, with a minimum starting value of 2.0 ng/mL)
  * Radiological progression in soft-tissue lesions according to PCWG3 modification of RECIST v1.1 criteria
  * Progression of bone disease (defined as ≥2 new bone lesions according to PCWG3 bone scan criteria).

Exclusion Criteria:

* Participants who have any of the following tumor lesions which are PSMA negative AND meet the size criteria below are excluded as determined by the site investigator. A PSMA-negative lesion for eligibility purposes must have activity equal to or less than the liver by visual assessment of the screening PSMA PET/CT scan using the study-designated PSMA PET/CT tracers. A PSMA-negative metastatic lesion should not correspond to a normal tissue structure or benign lesion.

  * a. Any single or multiple lymph node(s) ≥2.5cm in the short axis.
  * b. Any solid organ metastasis (e.g., lung, liver, adrenal glands, etc.) that is ≥1 cm in the short axis.
  * c. Any bone metastasis with a soft tissue component ≥ 1cm in short axis with the soft tissue component being PSMA-negative. PSMA-negative osseous metastases without a soft tissue component do not exclude a participant.
  * d. Predominantly necrotic lesions with greater than 1cm of enhancing tissue on contrast-enhanced Computer tomography / magnetic resonance imaging (CT/MRI).
* Prior systemic anticancer therapy including chemotherapy, NAAD, biologic therapy, immunotherapy, or investigational therapies within 4 weeks of the start of study intervention, except luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH). Start of study intervention is allowed in shorter timeframes if 5 half-lives of the prior drug(s) have elapsed.
* Prior radiopharmaceutical treatment using actinium-225.
* Other prior radiopharmaceutical treatments:

  * Dose escalation and Dose expansion Groups A and B: Prior treatment with a radiopharmaceutical is prohibited.
  * Dose expansion Group C: Prior treatment with a radiopharmaceutical is prohibited with the following exceptions: Prior treatment with radium-223 dichloride more than 3 months before the start of study intervention is permitted; and prior treatment with 177Lu PSMA more than 6 weeks before the start of study intervention is required.

Note: Participants who have discontinued 177Lu-PSMA treatment due to intolerance or loss of initial response are excluded from Group C.

* Prior definitive therapy (radiotherapy or surgery) completed less than 6 weeks before the start of study intervention. Note that palliative radiotherapy completed less than 6 weeks before the start of study intervention will be allowed if: (i) no more than 10% of the participants' bone marrow is irradiated, (ii) it does not encompass all potential target/measurable lesions for participants in dose expansion.
* Toxic effects of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 from prior anticancer therapy not yet stabilized or where significant post-treatment toxicities have been observed. Chronic toxic effects of CTCAE Grade ≤2 from prior anticancer therapy where no further resolution is expected do not require exclusion with agreement between the Investigator and Sponsor (e.g., chemotherapy-induced neuropathy, fatigue, alopecia, anorexia, etc.).
* Dose Expansion Group A and B: Presence of \>3 liver metastases, any diffuse liver metastasis, or PSMA-non-avid liver metastasis (uptake is lower or equal compared to healthy liver tissue).

Dose Expansion Group C: Presence of any liver metastasis (Bakht et al. 2023).

Where this trial is running

Duarte, California and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Castration-resistant Prostate Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.