utetium-177-anti-Programmed Cell Death-Ligand 1 single domain antibodies (177Lu-anti-PD-L1 sdAb) in metastatic non-small cell lung cancer
- Conditions
- Metastatic Non-small Cell Lung CancerCancer - Lung - Non small cell
- Registration Number
- ACTRN12623000959673
- Lead Sponsor
- Radiopharm Theranostics Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 23
Inclusion criteria
To be eligible for study, a participant must meet all of the following inclusion criteria:
1. Willing and able to provide informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures.
2. Adult participants greater than or equal to 18 years of age.
3. Participants with a documented history of histopathological confirmed metastatic NSCLC that is unresectable, progressive and for which standard treatment measures are no longer effective.
4. 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 antibody.
- 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 risk of adverse drug effects and/or interfere with the integrity of study outcome.
5. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
6. Participants must have a life expectancy of >4 months in the opinion of the Investigator.
7. 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 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 sterilisation should be considered for further investigation with luteinising hormone (LH) and follicle stimulating hormone (FSH) levels to confirm serological post-menopausal status.
8. 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.
9. 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.
10. 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.
11. For Phase I: Participants must have positive lesion(s) by 177Lu-RAD204im Single Photon Emission Computer Tomography (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 Assoc
Exclusion criteria
A participant who meets any of the following exclusion criteria must be excluded from study:
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 1 from prior anti-cancer therapy (except alopecia). Participants with > Grade 1 toxicity from prior anti-cancer 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.
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 (calculated using Cockcroft-Gault formula, or measured) < 60 mL/min or serum creatinine >1.5 x upper limit of normal (ULN)
• Platelet count of < 75 x 10^9/L
• Absolute neutrophil count (ANC) < 1.0 x 10^9/L
• Haemoglobin < 9 g/dL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x ULN, or > 5 x ULN for patients with known liver metastases
• Total bilirubin > 1.5 x ULN, except for patients with documented Gilbert’s syndrome who are eligible if total bilirubin is less than or equal to 3 x ULN
• For participants not taking warfarin or other anticoagulants: international normalised ratio (INR) less than or equal to 1.5 or prothrombin time (PT) less than or equal to 1.5 x ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) less than or equal to 1.5 x 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.
7. Patients requiring blood product transfusion within 4 weeks of first dose of 177Lu-RAD204tr are not eligible to participate.
8. Clinically significant cardiovascular disease including but not limited to:
• Unstable angina or acute myocardial infarction within 6 months prior to screening
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association (NYHA) grade greater than or equal to 2)
• Uncontrolled arterial hypertension or unstable clinically significant arrhythmia
• Known left ventricular ejection fraction (LVEF) < 50%
• QTcF > 470 msec for females and QTcF > 450 msec for males on screening electroc
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method