RAD202: Testing a new targeted radioactive treatment that uses specialised imaging and treatment for people with advanced HER2-positive or HER2-low solid cancers.Phase 0/1 Study of the Safety and Tolerability of 177Lu-RAD202, a Lutetium-177 Radiolabeled Single Domain Antibody Against Human Epidermal Growth Factor Receptor 2 in Patients With Advanced Solid Tumours

Exclusion

1. Participants who have any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or nonmelanoma 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.
2. 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.
3. Residual toxicity Grade ≥ 2 from previously administered therapy (except for alopecia).

4. Inadequate organ functions as reflected in laboratory parameters:

   • Creatinine clearance or Body Surface Area (BSA) adjusted Estimated glomerular filtration rate (eGFR) (calculated using any clinically validated formula, preferably Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or measured) < 60 mL/min
   • Platelet count of < 80 x 109/L
   • Absolute neutrophil count (ANC) < 1.5 x 109/L
   • Haemoglobin < 9 g/dL
   • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x upper limit of normal (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 normalized ratio (INR) ≥ 1.5 or prothrombin time (PT) ≥ 1.5 × ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≥1.5 × 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 intended therapeutic range of the anticoagulant.

5. 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)
   • QT interval corrected for heart rate using Fridericia's formula (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%. (LVEF may be performed either by echocardiogram or other appropriate imaging modalities such as nuclear cardiac imaging (MUGA) or MRI).
6. 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
7. Pregnant or lactating women

8. Participants who are receiving any other investigational agents

   The following exclusion criteria applies to participants in Phase 1 (Treatment Period):

9. 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.
10. Has had or is scheduled to have major surgery ≤ 28 days prior to the first dose of 177Lu-RAD202tr. Surgical procedures not considered to put participants at higher risk of AEs and/or interfere with the integrity of study outcome may be allowed on a case-by-case basis in discussion with the Sponsor.
11. Positive status for human immunodeficiency virus (HIV).
12. 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.
13. Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities.
14. Any uncontrolled intercurrent illness or clinically significant uncontrolled condition(s), including but not limited to active bacterial, fungal, or viral infections requiring systemic therapy.