Human Epidermal Growth Factor Receptor 2 (HER2) Antibody Therapy with Lutetium-177 in Patients with Advanced Solid Tumours.

Exclusion Criteria28

• Participants who have any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer. Participants with a history of malignancies of low recurrence potential who have received curative-intent therapy may be approved on a case-by-case basis in discussion with the study Sponsor, if it is determined not to put the participant at an increased risk of adverse drug effects and/or interfere with the integrity of study outcome.
• Participants who have any medical condition that would, in the Investigator’s judgment, prevent the participant’s full participation in the clinical study due to safety concerns or compliance with clinical study procedures such as participants with severe claustrophobia who are unresponsive to oral anxiolytics, participants with low back pain who cannot lie comfortably on an imaging table, participants who are hyperactive or hyperkinetic such that they cannot tolerate lying still for multiple time-point imaging procedures, etc.
• Residual toxicity Grade >= 2 from previously administered therapy (except for alopecia).
• Inadequate organ functions as reflected in laboratory parameters:
• Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 60 mL/min.
• Platelet count of < 100 x 10^9/L
• Absolute neutrophil count (ANC) < 1.5 x 10^9/L
• Haemoglobin < 9 g/dL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x ULN, or > 5 x ULN for patients with known liver metastases
• Total bilirubin > 1.5 x ULN, except for participants with documented Gilbert’s syndrome who are eligible if total bilirubin <= 3 x ULN
• For participants not taking warfarin or other anticoagulants: international normalised ratio (INR) <=1.5 or prothrombin time (PT) <= 1.5 x ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) <= 1.5 x ULN. Participants taking warfarin must be on a stable dose that results in a stable INR <3.5. Among participants receiving other anticoagulant therapy, PT or aPTT must be within the ntended therapeutic range of the anticoagulant.
• Significant cardiovascular disease including:
• Unstable angina and/or myocardial infarction within 6 months prior to screening
• New York Heart Association Class II or greater congestive heart failure
• Clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block)
• QTcF > 470 msec for females and QTcF > 450 msec for males on screening electrocardiogram (ECG) or congenital long QT syndrome
• Uncontrolled hypertension
• Known LVEF < 50%
• History of uncontrolled allergic reactions and/or have hypersensitivity to anti-HER2 monoclonal antibodies, kanamycin A or aminoglycoside therapies, or other excipients that may induce hypersensitivity
• Pregnant or lactating women
• Participants who are receiving any other investigational agents
• Major surgery within 4 weeks prior to first dose of 177Lu-RAD202tr. Exceptions may be approved on a case-by-case basis in discussion with study Sponsor, if it is determined not to put the participant at an increased risk of adverse drug effects and/or interfere with the integrity of study outcome.
• Received anti-cancer therapy, including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy or investigational device, within 28 days (or 5 half-lives for biologic/non-cytotoxic agents, whichever is shorter), prior to the first dose of 177Lu-RAD202tr.
• Has had or is scheduled to have major surgery <=28 days prior to the first dose of 177Lu-RAD202tr. Elective surgical procedures not considered to put participants at higher risk of AEs may be allowed on a case-by-case basis in discussion with the Sponsor.
• Positive status for human immunodeficiency virus (HIV).
• Active or chronic hepatitis B or C. Chronic hepatitis B or hepatitis C with undetectable viral loads on stable suppression therapy may be allowed on a case-by-case basis in discussion with study Sponsor.
• Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities.
• Any uncontrolled intercurrent illness or clinically significant uncontrolled condition(s), including but not limited to active bacterial, fungal, or viral infections requiring systemic therapy.