Advanced Metastatic Castration-resistant Prostate Cancer Clinical Trial
— PAnTHAOfficial title:
A Phase 1 Open-label, First-in-human, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of 225Ac-PSMA-Trillium in Participants With Advanced Metastatic Castration-resistant Prostate Cancer (mCRPC)
Researchers are looking for a better way to treat men who have metastatic castration-resistant prostate cancer (mCRPC). mCRPC is a cancer of the prostate (male reproductive gland found below the bladder) that has spread to other parts of the body. This type of prostate cancer does not respond to hormone treatment used to lower the level of testosterone, a male sex hormone, to prevent cancer from growing. The study treatment 225Ac-PSMA-Trillium, also called BAY3563254, is under development to treat advanced metastatic castration-resistant prostate cancer. It works by binding to PSMA and giving off radiation that can damage cancer cells and stop them from growing. The main purpose of this first-in-human study is to learn: - How safe is BAY3563254 in participants. - What is the recommended dose of BAY3563254 that is safe and works well that will be further tested in Part 2 of the study. - How well does BAY3563254 work in participants. To answer this, the researchers will look at: - The number and severity of medical problems including serious medical problems that participants experience after taking BAY3563254 - The number of dose-limiting toxicities (DLT) at each dose level. A DLT is a medical problem caused by a drug that is too severe to continue the use of that specific dose. - The number of participants whose cancer completely disappears (complete response) or reduces by at least 30% (partial response) after taking the treatment (also known as objective response rate (ORR)) - The number of participants who have a decrease in the levels of PSA* by at least 50% in their blood (also known as PSA50). PSA is a protein made by the prostate gland. High levels of PSA may indicate the presence of prostate cancer. - Participants' best response to treatment based on their PSA levels (also known as the best overall PSA response). The study will have two parts. The first part, called dose escalation, is done to find the most appropriate dose of BAY3563254 for use in the second part of the study. For this, each participant will receive one of different increasing amounts of BAY3563254. They will take BAY3563254 as an injection into a vein. All participants in the second part of the study, called dose expansion, will receive the most appropriate dose of BAY3563254 that was identified from the first part of the study. Participants in this study will take the study treatment once every 6 weeks, which is known as a treatment cycle. Each participant will have up to 4 of these treatment cycles, if the participant benefits from the treatment. Each participant will be in the study for approximately 6 years, including a screening phase of up to 30 days, 6 months of treatment depending on the participant's benefit, and a follow up phase of 60 months after the end of treatment. In addition, substudies performed during both dose escalation and dose expansion parts of the study will evaluate: - the clearance of radioactivity from the body over time - the doses of radiation that are delivered to normal organs and tumors - the ability of an experimental agent (Tris-POC) to decrease the amount of radiation absorbed by normal organs. During the study, the doctors and their study team will: - take blood and urine samples - check vital signs such as blood pressure, heart rate, and body temperature - examine heart health using electrocardiogram (ECG) - take tumor samples if required - check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and bone scan - check the tumor status using PET (positron emission tomography) - check the amount of radiation absorbed by tumors and normal organs using SPECT/CT (single-photon emission tomography and computed tomography scan) - ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study. The treatment period ends with a visit in 6-12 weeks after the last BAY3563254 dose. About 6-12 weeks after the last dose and every 6 weeks thereafter, the study doctors and their team will check the participants' health and any changes in their cancer. This active follow-up period ends after 18 months. The long-term follow-up period will start after the end of the active follow-up visit and will continue for up to 60 months after the the last BAY3563254 dose. Participants will be contacted, typically by phone call or clinic visit, approximately every 12 weeks after the end of active follow-up.
| Status | Recruiting |
| Enrollment | 118 |
| Est. completion date | May 24, 2031 |
| Est. primary completion date | June 14, 2027 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - mCRPC with pathological confirmation of adenocarcinoma without small-cell or neuroendocrine features. - Documented progressive mCRPC per PCWG3, defined when at least one of the following criteria is met: - 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 1.0 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) - 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 any taxane regimens 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 - Prior treatment with 177Lu-PSMA more than 6 weeks before the start of study treatment is required for participants in Dose Expansion Group C. - 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 treatment, as indicated below. Note that blood transfusions (red blood cells or platelets) and administration of G-CSF or GM-CSF are prohibited within 21 days prior to screening for the below bone marrow-related parameters. - 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), except if 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 serum creatinine =1.5 x ULN - Participants must have at least one PSMA-positive (prostate-specific membrane antigen) 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. 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) =2.5 cm 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 = 1 cm 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 1 cm of enhancing tissue on contrast-enhanced computed 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 treatment, except luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH). Start of study treatment is allowed in shorter timeframes if 5 half-lives of the prior drug(s) have elapsed. - Prior radiopharmaceutical treatment using 225Ac. - 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 treatment is permitted; and prior treatment with 177Lu PSMA more than 6 weeks before the start of study treatment is required. - Prior definitive therapy (radiotherapy or surgery) completed less than 6 weeks before the start of study treatment. Note that palliative radiotherapy completed less than 6 weeks before the start of study treatment 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) v5.0 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.). |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Institut Jules Bordet / Nuclear Medicine | Anderlecht | |
| Belgium | AZ Groeninge Campus Kennedylaan - Urology | Kortrijk | |
| Canada | Juravinski Cancer Centre - Clinical Trials Department | Hamilton | Ontario |
| Canada | Centre Hospitalier de l'Universite de Montreal (CHUM) - Hopi | Montreal | Quebec |
| Canada | British Columbia Cancer Agency-Vancouver Centre | Vancouver | British Columbia |
| United Kingdom | University College London Hospitals NHS Foundation Trust | London | |
| United Kingdom | Royal Marsden NHS Trust (Surrey) | Sutton | Surrey |
| Lead Sponsor | Collaborator |
|---|---|
| Bayer |
Belgium, Canada, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Dose Escalation and Dose Expansion: Incidence of TEAEs (including TESAEs) | TEAE: Treatment-emergent adverse event TESAE: Treatment-emergent serious adverse event | After the first administration of study intervention up to 42 days after the last dose of study intervention | |
| Primary | Dose Escalation and Dose Expansion: Severity of TEAEs (including TESAEs) | After the first administration of study intervention up to 42 days after the last dose of study intervention | ||
| Primary | Dose Escalation: Incidence of DLTs | DLT: Dose-Limiting Toxicities | Up to and including Cycle 3 (each cycle is 42 days) | |
| Primary | Dose Escalation and Dose Expansion: ORR by PCWG3 guideline based on Investigator review | ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per PCWG3 guidelines as assessed by the Investigator. | Up to 18 months after end of treatment | |
| Primary | Dose Escalation and Dose Expansion: PSA50 response | PSA50 response is defined as a =50% decline in PSA value from baseline (Cycle 1 Day 1). | At 12 weeks or later (up to 18 months after end of treatment) | |
| Primary | Dose Expansion: Best overall PSA response | Best overall PSA response corresponds to the maximum percentage decline or the minimum percentage increase (if no decline) in PSA value from baseline (Cycle 1 Day 1). | Up to 18 months after end of treatment | |
| Secondary | Dose Expansion: Recommended dose for further clinical development | Up to 18 months after end of treatment | ||
| Secondary | Dose Expansion: Recommended dose regimen for further clinical development | Up to 18 months after end of treatment | ||
| Secondary | Dose Escalation and Dose Expansion: Radiologic progression-free survival (rPFS) by PCWG3 based on Investigator review | rPFS is defined as the time from the start of study treatment to the date of first observed disease progression (Investigator's radiological assessment by PCWG3) or death due to any cause, if death occurs without progression is documented. | Up to 18 months after end of treatment | |
| Secondary | Dose Escalation and Dose Expansion: Duration of response (DOR) by PCWG3 based on Investigator review | DOR is defined as the time from the first documented objective response of PR or CR by PCWG3, whichever occurs earlier, to disease progression or death (if death occurs without progression is documented). | Up to 18 months after end of treatment | |
| Secondary | Dose Escalation and Dose Expansion: Duration of PSA50 response | Duration of PSA50 response is defined as the time from the first documented PSA50 response to PSA progression by PCWG3 or death (if death occurs without progression is documented). | Up to 18 months after end of treatment | |
| Secondary | Dose Escalation and Dose Expansion: Cmax of 225Ac | Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle) | ||
| Secondary | Dose Escalation and Dose Expansion: AUC and AUC(0-tlast) of 225Ac | Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle) | ||
| Secondary | Dose Escalation and Dose Expansion: Cmax of PSMA-Trillium-macropa peptide | Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle) | ||
| Secondary | Dose Escalation and Dose Expansion: AUC and AUC(0-tlast) of PSMA-Trillium-macropa peptide | Cycle 1, cycle 2 (From pre-dose up to Day 36 post-dose for each cycle) |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Terminated |
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