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

Prior treatment

• History of prior organ transplant.
• Residual toxicity ≥ Grade 2 from prior anti-cancer therapy (except alopecia). Patients with Grade 2 or higher toxicity due to prior treatment may be allowed on a case-by-case basis in discussion with the study Sponsor.
• Received anti-cancer therapy, including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy or investigational device, within 28 days prior to the first dose of 177Lu-RAD204tr.
• 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.
• Has had or is scheduled to have major surgery \< 28 days prior to the first dose of 177Lu-RAD204tr.

Other illness

• Any other known, active malignancy, except for treated cervical intraepithelial neoplasia or non-melanoma skin cancer.
• 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
• History of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics
• Clinically significant cardiovascular disease
• Positive status for human immunodeficiency virus (HIV).
• Active or chronic hepatitis B or C.
• 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).

Lab values

• 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 \< 100 × 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
  • Total bilirubin \> 1.5 × ULN, except for patients with documented Gilbert's syndrome who are eligible if total bilirubin ≤ 3 × 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.

Other

• Patients requiring blood product transfusion within 4 weeks of first dose of 177Lu-RAD204tr are not eligible to participate.
• Participation in any other investigational trial
• Pregnant or lactating women.

• Adult participants ≥ 18 years of age.
• Participants with a documented history of histopathologically confirmed relapsed/refractory locally advanced, inoperable or metastatic NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, endometrial cancer or any cancer that is known to be MMR deficient or MSI high with documented disease progression during or after their most recent line of anticancer therapy. Participants must be refractory to or have refused standard of care therapy or have no standard of care therapy available that is likely to provide clinical benefit.
• Participants with PD-L1 positive NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, endometrial cancer or any cancer that is known to be MMR deficient or MSI high:
  • If the participant tumour's PD-L1 expression status is unknown, PD-L1 positivity will be determined by IHC testing using a validated test (tumour tissue can be obtained from archived samples or from a freshly obtained biopsy).
• Must have at least 1 measurable target lesion according to RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Participants must have a life expectancy of ≥ 4 months in the opinion of the Investigator.
• Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (β-hCG) test and must not be breastfeeding.
• WOCBP must agree to use a highly effective method of contraception
• Participants with previously treated brain metastases are eligible to participate if:
  • they are neurologically and radiologically stable (no evidence of progression by imaging; same imaging modality \[magnetic resonance imaging (MRI) or computed tomography (CT) scan\] must be used for each assessment) for at least 28 days prior to the first dose of 177Lu-RAD204,
  • do not require steroids to treat associated neurological symptoms, and • have no history of leptomeningeal disease or spinal cord compression.
  • Participants with active brain metastases who have not received brain-directed therapy such as radiotherapy are not eligible to enroll.
• Participants must have positive lesion(s) identified by 177Lu-RAD204 imaging dose SPECT/CT.