Phase 0/1 Study of the Safety and Tolerability of 177Lu-RAD204, a Lutetium-177 Radiolabelled Single Domain Antibody Against Programmed Cell Death-Ligand 1 in Patients with Metastatic Solid Tumours.

ACTRN 12623000959673

Brief Summary

This study is evaluating the safety and properties of 177Lu-RAD204, a PD-L1 antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses joined to a radioactive lutetium isotopea radioactive substance, usually belonging to nuclear medicine, that is used for testing, imaging and/or treatment of cancer.

Intervention/Treatment

• Drug: 177Lu-RAD204

Inclusion Criteria

To be eligible for study, a participant must meet all of the following inclusion criteria:

1. Willing and able to provide informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. prior to start of any study procedures and assessments and must be willing to comply with all study procedures.
2. Adult participants = 18 years of age.
3. Participants with a documented history of histopathologically confirmed metastatic NSCLC, SCLC, TNBC, cutaneous melanomaa type of cancer that develops from melanocytes, which are the cells that produce pigment generally in the skin (but can develop in other areas of the body), HNSCC, and endometrial cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs 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 (including PD-1/PD-L1 inhibitors), or have no standard of care therapy available that is likely to provide clinical benefit.
4. Participants with PD-L1 positive NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, and endometrial cancer:
   • If the participant tumour’s PD-L1 expression status is unknown, PD-L1 positivity may be determined in a pre-screening step whereby the participant may be approached to provide written informed consent to have their tumoura tissue mass that forms from groups of unhealthy cells tissuea group of cells that work together to perform a function undergo IHC testing as determined by a validated test (tumour tissue may be obtained from archived samples or from a freshly obtained biopsyremoval of a section of tissue to analyse for cancer cells).
   • Any number of prior treatment lines are allowed.
5. Must have at least 1 measurable target lesion according to RECIST version 1.1.
6. Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status = 2.
7. Participants must have a life expectancy of = 4 months in the opinion of the Investigator.
8. Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (ß-hCG) test and must not be breastfeeding. WOCBP are defined as those who are not surgically sterile or post-menopausal. Female participants will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Female participants < 50 years old who meet the criteria for post-menopausal status without previous surgical sterilisation should be considered for further investigation with luteinising hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body (LH) and follicle stimulating hormone (FSH) levels to confirm serological post-menopausal status.
9. WOCBP must agree to use a highly effective method of contraception during the study and for 14 days after the last injection of 177Lu-RAD204im and/or 6 months after the last dosethe amount of medication taken of 177Lu-RAD204tr, whichever occurs later. Acceptable methods of contraception are described in Section 13.3 of the Protocol.
10. Male participants who are able to father a child must agree to avoid impregnating a partner and to adhere to a highly effective method of contraception during the study and for 14 days after the last injection of 177Lu-RAD204im and/or 6 months after the last dose of 177Lu-RAD204tr, whichever occurs later. All male participants must agree to not donate sperm during the study and for 14 days after the last injection of 177Lu-RAD204im and/or 6 months after the last dose of Lu-RAD204tr, whichever occurs later. Acceptable methods of contraception are described in Section 13.3 of the Protocol.
11. Participants with previously treated brain metastases are eligible to participate if:
    • they are neurologically and radiologically stable (no evidence of progression by imagingtests that create detailed images of areas inside the body; 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.
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.