A Study to Learn How Safe the Study Treatment Actinium-225-macropa-pelgifatamab (BAY3546828) is, How it Affects the Body, How it Moves Into, Through and Out of the Body, and About Its Anticancer Activity in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)

Launched by BAYER · Sep 18, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called actinium-225-macropa-pelgifatamab (also known as BAY3546828) for men with advanced metastatic castration-resistant prostate cancer (mCRPC), which is a type of prostate cancer that has spread to other parts of the body and does not respond to standard hormone therapies. The main goals of the study are to determine how safe this treatment is, how it affects the body, how well it works against the cancer, and the best dose to use. Participants will receive the treatment through an infusion into a vein and will be monitored closely by the study team for any side effects and changes in their cancer status through various tests and imaging techniques.

To be eligible for this trial, participants must have mCRPC confirmed by a doctor and have previously received certain treatments, such as hormone therapy or chemotherapy. They should also have a level of testosterone that is low enough and at least one area of cancer that can be seen on special scans. Throughout the study, participants can expect to be involved for up to six years, which includes treatment cycles and follow-up visits to assess their health and response to the treatment. This trial aims to find better options for men facing limited treatment choices for their cancer.

Gender

MALE

Eligibility 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).