Phase 1 Trial of ITM-22 in Patients with Prostate-Specific Membrane Antigen (PSMA)-positive Progressive Metastatic Castration Resistant Prostate Cancer

Exclusion Criteria40

• All participants will be excluded from participation in the trial if one or more of the following criteria are met:
• Having received more than 2 previous doses of PSMA-targeted radiopharmaceutical therapy (RPT). Last targeted RPT dose should have been administered greater than or equal to 12 weeks prior to enrolment to be eligible
• Last treatment with external beam radiotherapy, or with radioactive bone-seekers should have been administered greater than or equal to 12 weeks prior to enrolment
• Having received more than 3 systemic lines of therapy overall (luteinizing hormone-releasing hormone (LHRH) analogues excluded), regardless of the castration sensitivity status
• One or more of the following PSMA PET/CT negative lesion types:
• a. greater than or equal to 1.0 cm soft tissue component in a bone metastatic lesion
• b. greater than or equal to 2.5 cm lymph node metastatic lesion
• c. greater than or equal to 1.0 cm solid organ metastatic lesion
• Any systemic anti-cancer therapy within 30 days prior to trial enrolment (except Androgen receptor axis targeted therapy (ARAT) for which 7 days are sufficient and except LHRH analogues without time restriction)
• Any investigational therapeutic agents within 30 days or 5 half-life periods, whichever is longer, prior to trial enrolment
• Major surgery within 30 days prior to trial enrolment
• Received a live attenuated vaccine within 30 days prior to trial enrolment
• Known hypersensitivity to the components of the trial therapy or its analogues.
• History of brain metastases or leptomeningeal metastases. A scan to confirm the absence of brain metastases is not required if there is no history of this
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression unless appropriately treated beforehand and clinically stable for greater than or equal to 30 days
• Severe uncontrolled non-malignant disease (e.g., psychiatric, infectious, autoimmune, metabolic or dementia), that may interfere with the objectives of the trial or with the safety or compliance of the participant, as judged by the Investigator. Specific attention should be paid to the risk of bleeding that is not properly treated and controlled, such as epistaxis, oesophageal varices or gastrointestinal bleeding
• Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with such a prior history of other malignancy that has been adequately treated and who have been disease free for at least 3 years are eligible, as are, with no time restriction, participants with adequately treated low-grade malignancies which have low risk of recurrence such as non-melanoma skin cancer or superficial bladder cancer
• Renal, hepatic, cardiovascular, or haematological organ dysfunction, potentially interfering with the safety of the trial treatments, including the following:
• a. Renal:
• i. Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021 formula [local laboratory])
• ii. Urinary tract obstruction or hydronephrosis unless effective catheterisation is in place
• b. Hepatic:
• i. Total bilirubin > 2 × upper limit of normal (ULN) or > 3 × ULN for participants with Gilbert’s disease or liver metastases
• ii. Albumin < 30 g/L
• iii. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × ULN, with the exception that participants with liver metastasis must have AST and/or ALT less than or equal to 5 × ULN
• c. Haematologic:
• i. Platelet count less than or equal to 100 × 109/L
• ii. Absolute neutrophil count (ANC) < 1.5 × 109 cells/L
• iii. Haemoglobin concentration < 6.2 mmol/L (< 10.0 g/dL; measured at least 30 days after a previous transfusion if any given to the participant)
• d. Cardiovascular:
• i. Congestive heart failure (New York Heart Association [NYHA] classification III and IV), unstable angina
• ii. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds
• iii. History or current diagnosis of ECG abnormalities indicating significant risk of safety for trial participants
• Any ongoing greater than or equal to Grade 2 toxicities related to prior therapies, with the exception of alopecia of any grade, stable treated electrolyte abnormalities on replacement and Grade 2 peripheral neuropathy from previous standard or investigational therapies (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0)
• Male participants with female partners of childbearing potential, unless:
• a. willing to practice full and true sexual abstinence, or
• b. are surgically/permanently sterile (bilateral tubal occlusion, hysterectomy, or vasectomy), or
• c. are willing to practice highly effective contraception in combination with a barrier method of contraception (e.g., condom). Contraception methods that are considered highly effective are: oral or non-oral (injected or implanted) non-oestrogen progesterone-based hormonal method; oral, intravaginal, or transdermal combined oestrogen and progesterone-based hormonal methods; and/or intrauterine device, and/or intrauterine hormone-releasing system. Sexual abstinence or the contraception methods described above must be followed throughout the entire trial period and for at least 14 weeks (half-lives of actinium-225 is 9.92 days) after the last treatment cycle
• Current unmanageable urinary incontinence preventing safe administration of the IMP, in the Investigator’s opinion
• Not able to declare meaningful informed consent on his own (e.g., with legal guardian for mental disorders) or any other vulnerable population to that sense (e.g., persons institutionalised, incarcerated etc.)