177LU-RHPSMA-10.1 for Metastatic castration-resistant prostate cancer

Inclusion criteria

• {"criterion_text":"- 01. Male subjects, 18 years of age or older."}
• {"criterion_text":"- 08. At least 28 days or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinising Hormone-releasing Hormone or GnRH)."}
• {"criterion_text":"- 09. Resolution of all previous treatment-related toxicities to CTCAE Version 5.0 Grade of ≤1 (except for chemotherapy-induced alopecia and Grade 2 peripheral neuropathy or Grade 2 urinary frequency which are allowed)."}
• {"criterion_text":"- 10. Prior major surgery must be at least 12 weeks prior to study entry."}
• {"criterion_text":"- 11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months."}
• {"criterion_text":"- 14. Study phase-specific inclusion criteria: a) For Phase 1 mCRPC only: Subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide) and at least 1 course (but no more than 2 courses) of taxane-based chemotherapy. b) For Phase 2 mCRPC only: Subjects who have experienced disease progression on or after at least 1 NAAD (e.g. abiraterone, enzalutamide, apalutamide, darolutamide), but have not received previous taxane-based chemotherapy for the treatment of mCRPC. • Prior NAAD can be given as part of doublet or triplet therapy during treatment for metastatic hormone sensitive prostate cancer, or during the castrate resistant phase of disease. • Prior chemotherapy as part of the treatment of metastatic hormone sensitive disease is permitted. • Prior first-generation androgen receptor inhibitors (i.e. bicalutamide) are permitted but do not count as prior NAAD for eligibility in this trial. Notes: Subjects must have progressive mCRPC. Disease progression is defined by the “criteria for progression at trial entry” (Table 3 in PCWG3 guidelines; Scher 2016; Appendix 2 to protocol). Taxane exposure is defined as a minimum of 2 cycles."}
• {"criterion_text":"- 12. Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline: For Phase 1 only: • Platelet count ≥150 × 10^9/L • White blood cell (WBC) count ≥3.0 × 10^9/L • Neutrophil count of ≥1.5 × 10^9/L • Haemoglobin ≥10 g/dL • Estimated glomerular filtration rate (using Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation [2009]) (Levey 2009) ≥60 mL/min • Total bilirubin <1.5× ULN (except if confirmed history of Gilbert's disease) • Serum albumin ≥30 g/L • AST <2× the ULN • ALT <2× the ULN For Phase 2 only: Bone marrow reserve: • Platelet count ≥150 × 10^9/L • WBC count ≥3.0 × 10^9/L • Neutrophil count of ≥1.5 × 10^9/L • Haemoglobin ≥9 g/dL Renal: • Estimated glomerular filtration rate (using Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation [2009]) (Levey 2009) ≥60 mL/min Hepatic: • Total bilirubin <2 × the institutional ULN. For subjects with known Gilbert's Syndrome, ≤3 × ULN is permitted • AST <3 × the ULN (<5 × ULN in the presence of confirmed liver metastasis) • ALT <3 × the ULN (<5 × the ULN in the presence of confirmed liver metastasis) • Serum albumin ≥30 g/L"}
• {"criterion_text":"- 13. Male subjects must not father children or donate sperm during the study and for at least 6 months after the last study treatment. In addition, they must agree to use condoms and highly effective contraception for this same period to protect partners from any exposure to the IMP. For fertile males with partners who are women of childbearing potential, highly effective contraception should be used during the study and for at least 6 months after the last study treatment. Highly effective methods of contraception include: • combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) • intrauterine device • intrauterine hormone-releasing system • bilateral tubal occlusion • vasectomised partner • sexual abstinence, only where this is the preferred and usual lifestyle of the subject. A woman is considered of childbearing potential i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause. A man is only considered to be infertile if he has had bilateral orchidectomy or successful vasectomy with laboratory confirmed aspermia."}
• {"criterion_text":"- 02. Willing to provide signed and dated written informed consent form (ICF) prior to any study-specific procedures."}
• {"criterion_text":"- 03. Willing to comply with required lifestyle restrictions following administration of the IMP per local regulations."}
• {"criterion_text":"- 04. Histologically confirmed adenocarcinoma of the prostate."}
• {"criterion_text":"- 05. Serum testosterone levels <50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration. Note: If a sample has been taken within the last 3 months before the screening date and there has been no change to medication it can be used to confirm eligibility."}
• {"criterion_text":"- 06. Presence of disease target or non-target lesions (per RECIST v1.1) on CT/MRI and/or Presence of disease on full body 99mTc bone scan. Note: Imaging scans obtained no more than 28 days prior to informed consent may be used to determine imaging eligibility, if available for submission to the central reader"}
• {"criterion_text":"- 07. Positive disease expression of PSMA as confirmed on PSMA PET/CT scan. Note: For Phase 1 only: Positive disease is defined as having at least 1 PSMA-positive lesion of any size with higher uptake than normal liver using visual assessment. The lesion can be bone, lymph node or viscera. At least one PSMA-positive lesion should be visible on the CT/MRI and ≥1.5 cm in the short axis. Further details regarding the interpretation of the diagnostic images can be found in the Image Acquisition Guidelines. For Phase 2 only: Positive disease is defined as: • Having at least 1 PSMA-positive lesion of any size with a higher uptake than normal parotid using visual assessment. The lesion can be bone, lymph node or viscera, and • Having the majority of PSMA-expressing disease with equivalent or higher uptake than normal liver using visual assessment. PSMA PET/CT scans obtained no more than 28 days prior to informed consent may be used to determine PSMA eligibility, if available for submission to the central reader. Further details regarding this inclusion criterion can be found in the Image Review Charter."}

Exclusion criteria

• {"criterion_text":"- 01. Known hypersensitivity to the therapeutic IMP, PSMA PET/CT tracer, or diagnostic IMP (for Phase 1 only) or any of its constituents."}
• {"criterion_text":"- 10. Any uncontrolled significant medical, psychiatric, or surgical condition or laboratory finding that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results. For cardiac conditions, this includes, but is not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, and myocardial infarction diagnosed within 6 months prior to enrolment."}
• {"criterion_text":"- 11. Ongoing treatment with bisphosphonates for bone-targeted therapy. Exception: Subjects will be eligible if they have received a stable dose of bisphosphonates for at least 6 weeks prior to enrolment. These subjects must have had renal function monitored since initiation of bisphosphonate therapy, with a stable pattern observed, and must have an estimated glomerular filtration rate ≥ 60 mL/min."}
• {"criterion_text":"- 12. Severe urinary incontinence that would preclude safe disposal of radioactive urine."}
• {"criterion_text":"- 13. Single kidney, renal transplant, or any concomitant nephrotoxic therapy, that in the judgement of the investigator might put the subject at high risk of renal toxicity during the study."}
• {"criterion_text":"- 14. Based on the judgement of the investigator, clinically significant abnormalities on a single 12-lead electrocardiogram (ECG) at screening."}
• {"criterion_text":"- 15. Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys."}
• {"criterion_text":"- 16. Sponsor employees or investigator site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted."}
• {"criterion_text":"- 17. Previous treatment with any of the following: PSMA-targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation."}
• {"criterion_text":"- 18. Subjects with bilateral hip replacements or any significant metallic implants or objects, which may in the opinion of the investigator, affect image quality and/or dosimetry calculations (for Phase 1 only)."}
• {"criterion_text":"- 19. Transfusion of blood products for the sole purpose of meeting the eligibility criteria for this clinical study."}
• {"criterion_text":"- 02. Presence of PSMA-negative disease: Note: For Phase 1 only: defined as any large PSMA-negative lymph node >1 cm in the short axis and/or a PSMA-negative bone metastasis which has a significant soft tissue component suggesting ongoing disease activity and/or a PSMA-negative solid organ metastasis >1 cm in the long axis. In addition, subjects with significant low PSMA-expressing disease should be excluded. Further details are provided in the Image Acquisition Guidelines. For Phase 2 only: defined as any large PSMA- negative lymph node >2.5 cm in the short axis and/or a PSMA negative bone metastasis which has a significant soft tissue component suggesting ongoing disease activity and/or a PSMA-negative solid organ metastasis >1 cm in the long axis. Further details are provided in the Image Review Charter."}
• {"criterion_text":"- 20. Participation in other studies involving IMP(s) within 28 days or 5 half-lives (whichever is longer) prior to study entry and/or during study participation."}
• {"criterion_text":"- 03. Diffuse marrow infiltration of disease (‘superscan’ appearance on full body 99mTc bone scan). A superscan is defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake in relation to soft tissues along with absent or faint activity in the genitourinary tract and soft tissues due to diffuse bone/bone marrow metastases."}
• {"criterion_text":"- 04. Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression."}
• {"criterion_text":"- 05. Known history of haematological malignancy."}
• {"criterion_text":"- 06. Known history of central nervous system (CNS) metastases. Exception: Subjects with a history of CNS metastases who have received and completed therapy (e.g. surgery, radiotherapy), and are neurologically stable, asymptomatic and do not require corticosteroids or anti-convulsants to control neurological symptoms will be eligible. Discrete dural metastases are permitted but diffuse leptomeningeal disease is not. For subjects with a history of CNS metastases, baseline imaging and subsequent radiological imaging for assessing treatment response must include MRI or ceCT evaluation of the brain."}
• {"criterion_text":"- 07. Histological findings consistent with neuroendocrine phenotype of prostate cancer."}
• {"criterion_text":"- 08. Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment. Exception: Subjects with histopathologically confirmed prior malignancy that has been treated, and who have been disease-free for >3 years. Subjects with treated non-melanoma skin cancer and non-muscle invasive bladder cancer will be eligible."}
• {"criterion_text":"- 09. Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy. Where the clinical team judges that the subject’s hydronephrosis is not obstructing, and renal function meets the inclusion criteria, the subject may undergo 99mTc mercaptoacetyltriglycerine scanning during the screening period and if the result is non-obstructed, the subject can be eligible for the study."}

Primary endpoints

• {"endpoint_text":"- Phase 1: 1. Incidence of DLTs during the DLT observation period. The definition of DLTs in this study is described in protocol section 4.1.1.4.","definition_or_measurement_approach":"DLTs incidence during the predefined DLT observation period; the study protocol defines DLTs (see protocol section 4.1.1.4)."}
• {"endpoint_text":"- Phase 1: 2. Frequency and nature of treatment-emergent adverse events (TEAEs).","definition_or_measurement_approach":"TEAEs recorded and summarised by frequency and nature (standard safety reporting)."}
• {"endpoint_text":"- Phase 2: The number of subjects with an anti-tumour response defined as a ≥50% reduction in PSA level from baseline to the End of Treatment (EoT).","definition_or_measurement_approach":"Anti-tumour response measured as ≥50% reduction in PSA from baseline to EoT (PSA laboratory measurement comparisons)."}

Secondary endpoints

• {"endpoint_text":"- Phase 1: 1. Terminal half-life of activity concentrations in blood.","definition_or_measurement_approach":"Pharmacokinetic measurement of elimination half-life from blood activity concentrations."}
• {"endpoint_text":"- Phase 1: 2. Specific whole-body absorbed dose (Gy/GBq), specific absorbed dose to the tumour lesions (Gy/GBq), specific absorbed dose per organ (Gy/GBq) and cumulative absorbed organ and whole-body absorbed doses (Gy).","definition_or_measurement_approach":"Dosimetry assessments producing absorbed dose values (Gy/GBq and cumulative Gy) per organ, lesion and whole body."}
• {"endpoint_text":"- Phase 1: 3. Number of subjects with ≥50% reduction in PSA level from baseline at 12 weeks after first therapeutic IMP administration.","definition_or_measurement_approach":"Count of subjects achieving ≥50% PSA reduction at 12 weeks post first therapeutic IMP dose."}
• {"endpoint_text":"- Phase 1: 4. Number of subjects with best response in PSA level ≥50% from baseline to the end of the dosing period.","definition_or_measurement_approach":"Count of subjects whose best PSA response during dosing period is ≥50% reduction from baseline."}
• {"endpoint_text":"- Phase 1: 5. PSA Progression-free survival (PFS): Time interval from first cycle of therapeutic IMP administration to PSA progression as defined by the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria, or death, whichever comes first.","definition_or_measurement_approach":"Time-to-event (PSA PFS) per PCWG3 criteria or death."}
• {"endpoint_text":"- Phase 1: 6. Number of subjects who remain PSA progression-free at fixed 6-month intervals throughout the study.","definition_or_measurement_approach":"Counts at predefined 6-month timepoints of subjects without PSA progression."}
• {"endpoint_text":"- Phase 1: 7. Duration of response as defined by time interval from achieving a ≥50% reduction in PSA compared to baseline to the PSA returning to baseline or evidence of radiological progression, as defined by PCWG3, or death.","definition_or_measurement_approach":"Time from achieving ≥50% PSA reduction to PSA return to baseline, radiological progression, or death."}
• {"endpoint_text":"- Phase 1: 8. Radiographic PFS (rPFS): Time interval from first therapeutic IMP administration to the date when the first site of disease is found to progress radiographically, or death, whichever occurs first, as defined by PCWG3.","definition_or_measurement_approach":"Time-to-event (radiographic progression or death) per PCWG3."}
• {"endpoint_text":"- Phase 1: 9. Number of subjects who remain radiographic progression-free at fixed 6-month intervals throughout the study.","definition_or_measurement_approach":"Counts at 6-month intervals of subjects without radiographic progression."}
• {"endpoint_text":"- Phase 1: 10. Number of subjects with confirmed complete response (CR) or partial response (PR) based on PCWG3-recommended application of the Response Evaluation Criteria in Solid Tumours v1.1 (RECIST v1.1) criteria.","definition_or_measurement_approach":"Radiological response assessment per RECIST v1.1 as applied per PCWG3."}
• {"endpoint_text":"- Phase 1: 11. Evaluation of PSMA PET/CT defined disease response after 2 treatment cycles.","definition_or_measurement_approach":"PSMA PET/CT image-based response assessment after 2 cycles."}
• {"endpoint_text":"- Phase 1: 12. Overall survival at fixed 6 month intervals throughout the study.","definition_or_measurement_approach":"Overall survival counts and estimates at 6-month intervals."}
• {"endpoint_text":"- Phase 1: 13. Time to PSA progression: Time interval from first cycle of therapeutic IMP administration to PSA progression as defined by the PCWG3 criteria.","definition_or_measurement_approach":"Time-to-event (PSA progression) per PCWG3 criteria."}
• {"endpoint_text":"- Phase 1: 14. Time to radiographic progression: Time interval from first therapeutic IMP administration to the date when the first site of disease is found to progress radiographically as defined by PCWG3","definition_or_measurement_approach":"Time-to-event (radiographic progression) per PCWG3."}
• {"endpoint_text":"- Phase 2: 1. Number of subjects with ≥50% reduction in PSA level from baseline at 12 weeks after first IMP administration.","definition_or_measurement_approach":"Count of subjects meeting ≥50% PSA reduction at 12 weeks post first IMP."}
• {"endpoint_text":"- Phase 2: 2. PSA PFS: Time interval from first cycle of IMP administration to PSA progression as defined by PCWG3 criteria, or death.","definition_or_measurement_approach":"Time-to-event (PSA progression or death) per PCWG3."}
• {"endpoint_text":"- Phase 2: 3. Number of subjects who remain PSA progression-free at fixed 6-month intervals throughout the study.","definition_or_measurement_approach":"Counts at 6-month intervals of subjects without PSA progression."}
• {"endpoint_text":"- Phase 2: 4. Duration of response as defined by time interval from achieving a ≥50% reduction in PSA compared to baseline to the PSA returning to baseline or evidence of radiological progression, as defined by PCWG3.","definition_or_measurement_approach":"Time from ≥50% PSA reduction to PSA return to baseline, radiological progression, or death."}
• {"endpoint_text":"- Phase 2: 5. Radiographic PFS: Time interval from first cycle of IMP administration to the date when the first site of disease is found to progress radiographically, or death, whichever occurs first, as defined by PCWG3.","definition_or_measurement_approach":"Time-to-event (radiographic progression or death) per PCWG3."}
• {"endpoint_text":"- Phase 2: 6. Number of subjects who remain radiographic progression-free at fixed 6-month intervals throughout the study.","definition_or_measurement_approach":"Counts at 6-month intervals of subjects without radiographic progression."}
• {"endpoint_text":"- Phase 2: 7. Number of subjects with confirmed CR or PR based on PCWG3-recommended application of RECIST v1.1.","definition_or_measurement_approach":"RECIST v1.1-based radiological response assessments as applied per PCWG3."}
• {"endpoint_text":"- Phase 2: 8. Overall survival, defined as the time interval from first cycle of IMP administration to death.","definition_or_measurement_approach":"Time from first IMP to death (overall survival)."}
• {"endpoint_text":"- Phase 2: 9. Overall survival at fixed 6-month intervals throughout the study.","definition_or_measurement_approach":"Overall survival estimates and counts at 6-month intervals."}
• {"endpoint_text":"- Phase 2: 10. Time to PSA progression: Time interval from first cycle of IMP administration to PSA progression as defined by PCWG3 criteria.","definition_or_measurement_approach":"Time-to-event (PSA progression) per PCWG3."}
• {"endpoint_text":"- Phase 2:11. Time to radiographic progression: Time interval from first cycle of OG-toediening tot de datum waarop de eerste plaats van de ziekte radiografisch progressie vertoont, zoals gedefinieerd door PCWG3.","definition_or_measurement_approach":"Time-to-event (radiographic progression) per PCWG3."}
• {"endpoint_text":"- Phase 2: 12. Frequency and nature of TEAEs.","definition_or_measurement_approach":"AE collection and summarisation by frequency and type (safety reporting)."}
• {"endpoint_text":"- Phase 2: 13. Specific absorbed dose to the tumour lesions (Gy/GBq), specific absorbed dose per organ (Gy/GBq).","definition_or_measurement_approach":"Dosimetry measures of absorbed dose to lesions and organs (Gy/GBq)."}
• {"endpoint_text":"- Phase 2: 14. Changes in patient-reported outcomes (PROs) assessed by FACT-P. The PROs will be measured from baseline up to the EoT: • Change from baseline in FACT-P total score. • Proportion of subjects with improvement or worsening in the FACT-P total score and subscales. • Time to worsening in the FACT-P total score and subscales, defined as the time from first cycle of IMP administration to worsening, clinical progression, or death, whichever occurs first.","definition_or_measurement_approach":"PRO assessments using FACT-P: change from baseline, proportion improved/worsened, and time-to-worsening analyses up to EoT."}

Belgium

Earliest CTIS Part Ii Submission Date

10-07-2024

Latest Decision Or Authorization Date

13-11-2025

Processing Time Days

491

Number Of Sites

5

Number Of Participants

13

Netherlands

Earliest CTIS Part Ii Submission Date

10-07-2024

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

488

Number Of Sites

2

Number Of Participants

18

Germany

Earliest CTIS Part Ii Submission Date

10-07-2024

Latest Decision Or Authorization Date

23-02-2026

Processing Time Days

593

Number Of Sites

6

Number Of Participants

20

Primary sponsor

Full Name

Blue Earth Therapeutics Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Psi Cro AG

Responsibilities

Vendor Management, Translations, Trial Master File, SDTM, DSMB Management

Third parties

• {"country":"France","full_name":"Keosys","duties_or_roles":"Medical image analysis","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Radiopharmaceutical Imaging And Dosimetry LLC","duties_or_roles":"Medical image analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Psi Cro AG","duties_or_roles":"Vendor Management, Translations, Trial Master File, SDTM, DSMB Management","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Medpace Core Lab","duties_or_roles":"Medical image analysis","organisation_type":"Industry"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}