Brief Summary
This is a first-in-human, open-label study consisting of a Screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening Period, an Imagingtests that create detailed images of areas inside the body Period, and a Treatment Period in eligible non-small lung cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs patients who are positive for the biomarker PDL-1. The Screening period lasts up to 4 weeks. The Phase 0 (Imaging Period) is used to determine if patient’s tumor(s) are still positive for the biomarker, as well as radiation dosimetry with low dosethe amount of medication taken 177Lu-RAD204im (for a period of up to 2 weeks following the first injection of 177Lu-RAD204im), to assess the safety of the drug. Following the 2 week safety assessment, the subject is eligible to enter Phase I (Treatment Period) with gradual dose increases of 177Lu-RAD204tr. The Treatment Period lasts up to 3 cycles every 6 weeks, with additional extension to a maximum study dose interval of 12 weeks to be approved on a case-by-case basis in discussion with study Sponsor. During the Treatment Period, subjects will be assessed for both safety and treatment response using conventional images and clinical laboratory tests.
Intervention / Treatment
- Drug: 177Lu-RAD204
Inclusion Criteria:
- 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.
- Adult participants ≥ 18 years of age.
- Participants with a documented history of histopathological confirmed metastatic NSCLC that is unresectable, progressive and for which standard treatment measures are no longer effective.
- Participants with a documented history of PD-L1 positive NSCLC. Any number of prior treatment lines are allowed in this study, however at least one of the treatment line(s) must include an anti-PD(L)-1 antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses. Participants with any documented PD-L1 positivity by immunohistochemistry (IHC) without prior treatment with anti-PD(L)-1 antibody may be allowed on a case-by-case basis in discussion with study Sponsor, if it is determined not to put the participant at an increased riskthe possibility that something bad will happen of adverse drug effects and/or interfere with the integrity of study outcome.
- Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer 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 are defined as those who are not surgically sterile or post-menopausal. Female subjects will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Female subjects < 50 years old who meet the criteria for post-menopausal status without previous surgical sterilization should be considered for further investigation with luteinizing 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.
- 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 dose of 177Lu-RAD204tr, whichever occurs later. Acceptable methods of contraception are described the Protocol.
- Male subjects 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 subjects must agree to not donate sperm during the study and for 14 days after the last injection of 177Lu-RAD204im and/or 4 months after the last dose of Lu-RAD204tr, whichever occurs later. Acceptable methods of contraception are described in the Protocol.
- Subjects with previously treated brain metastases are eligible to participate if: they are clinically 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; and any neurologic symptoms returned to baseline. Note: Subjects with a history of leptomeningeal disease may not participate even if stable clinically.
- For Phase I: Participants must have positive lesion(s) by 177Lu-RAD204im SPECT/CT as described in Image Review Manual. Estimated total radiation dose to healthy organs derived from phase 0 dosimetry must not exceed dose constraints according to the American Association of Physicists in Medicine Quantitative Analysis of Normal Tissuea group of cells that work together to perform a function Effect in the Clinic (QUANTEC) and International Commission on Radiological Protection (ICRP), in discussion with study Sponsor.