177Lu-anti-PD-L1 sdAb in Metastatic Solid Tumors

Exclusion Criteria

• •12. For Phase I:
• •* Participants must have positive lesion(s) by 177Lu-RAD204im SPECT/CT per central review as described in Image Review Charter, and
• •* Participants without any positive lesion by 177Lu-RAD204im SPECT/CT, e.g. due to poor image quality, may be allowed to enrol on a case-by-case basis at the discretion of the Principal Investigator and in discussion with study Sponsor, provided the participant's tumour is known to express PD-L1.
• •1. History of prior organ transplant.
• •2. Any other known, active malignancy, except for treated cervical intraepithelial neoplasia or non-melanoma skin cancer. Patients 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 study Sponsor, if it is determined not to put the patient at an increased risk of adverse drug effects and/or interfere with the integrity of study outcome.
• •3. 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.
• •4. Residual toxicity ≥ Grade 2 from prior anti-cancer therapy (except alopecia).
• •5. History of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics, 177Lu-RAD204 or any of its excipients.
• •6. 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 × 109/L
• •* Absolute neutrophil count (ANC) \< 1.5 × 109/L
• •* Haemoglobin \< 9 g/dL
• •* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × ULN, or \> 5 × ULN for patients with known liver metastases
• •8. Clinically significant cardiovascular disease including but not limited to:
• •* Unstable angina
• •* Acute myocardial infarction within 6 months prior to screening
• •* New York Heart Association (NYHA) Class II or greater congestive heart failure (see Section 20.6)
• •* Clinically significant abnormalities in rhythm, conduction or morphology on resting ECG (e.g. complete left bundle branch block, third degree heart block)
• •* Uncontrolled hypertension
• •* Known LVEF \< 50%
• •* 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.
• •9. Participation in any other investigational trial at the time of informed consent signature.
• •10. Pregnant or lactating women.
• •11. 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-RAD204tr.
• •12. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-mediated AE.
• •NOTE: endocrine immune-mediated AEs that are controlled with replacement therapy are allowed.
• •13. Has had or is scheduled to have major surgery \< 28 days prior to the first dose of 177Lu-RAD204tr.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.
• •14. Positive status for human immunodeficiency virus (HIV).
• •15. 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.
• •16. Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities.
• •17. Any uncontrolled intercurrent illness or clinically significant uncontrolled condition(s), including but not limited to active bacterial, fungal, or viral infections requiring systemic therapy.