None listed
Conditions
Brief summary
This study is evaluating the safety and properties of 177Lu-RAD204, a PD-L1 antibody joined to a radioactive lutetium isotope. Who is it for? You may be eligible for this study if you are an adult patient with confirmed PD-L1 positive solid tumours including non small cell lung cancer (NSCLC), small cell lung cancer (SCLC), triple negative breast cancer (TNBC), cutaneous melanoma, head and neck squamous cell carcinoma (HNSCC) and endometrial cancer that is unresectable, progressive and for which standard treatment measures are no longer effective. Study details Participants will undergo a Screening Period of up to 4 weeks, followed by a Phase 0 (Imaging) Period for imaging and receiving a single injection of 177Lu-RAD204. If they are able to tolerate this in the following 2 week period, they will then proceed to a Phase I (Treatment) Period where they will be assigned a dose of 177Lu-RAD204 delivered every 6 weeks for 3 cycles. Blood sampling and imaging studies will be performed to determine how the participant is responding to 177Lu-RAD204. Additional treatment cycles (beyond 3 cycles) will be considered if participant is deemed to receive clinical benefit from 177Lu-RAD204 and approved by study Sponsor. Findings from this study will help determine a recommended dose of 177Lu-RAD204 for future exploration
Interventions
This study involves the use of investigational compound, 177Lu-RAD204 in patients with PD-L1 positive solid tumours. Among the tumour types to be included in this study are non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), triple negative breast cancer (TNBC), cutaneous melanoma, head and neck squamous cell carcinoma (HNSCC) and endometrial cancer. There will be 2 different phases in this study whereby Phase 0 (Imaging period) using 10 mCi of 177Lu-RAD204 and Phase I (treatment
This study involves the use of investigational compound, 177Lu-RAD204 in patients with PD-L1 positive solid tumours. Among the tumour types to be included in this study are non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), triple negative breast cancer (TNBC), cutaneous melanoma, head and neck squamous cell carcinoma (HNSCC) and endometrial cancer. There will be 2 different phases in this study whereby Phase 0 (Imaging period) using 10 mCi of 177Lu-RAD204 and Phase I (treatment period) where 2 different dose levels (30 mCi and 40mCi) of 177Lu-RAD204 will be explored. The investigational product/IP (177Lu-RAD204) given during Phase 0 will be indicated as 177Lu-RAD204im while the IP given during Phase 1 (treatment period) will be indicated as 177Lu-RAD204tr. For Phase 0, after undergo screening, if patient is deemed eligible, they will be taking 1 dose of 10mCi of 177Lu-RAD204im and if they tolerate the study drug after 2 weeks, they can roll-over to Phase 1 where patient will receive either 30mCi (dose level 1) or 40mCi (dose level 2) of 177Lu-RAD204tr every 6 weeks with a maximum of 3 doses given. Further treatment cycle will be considered if investigator deems that patient is receiving benefit from study drug, with sponsor approval. 177Lu-RAD204 will be administered as intravenous (IV) bolus injection under the supervision of the study Investigator or appropriately qualified delegate. Patient medical record will be used to monitor adherence to the intervention. The continuous safety evaluation will be performed by sponsor, medical monitor, the investigators. A DSMB (Data Safety Monitoring Board) or equivalent committee will be established for the determination of dose escalation and monitoring of dose-limiting toxicity (DLT) for all patients who received 177Lu-RAD204.
Sponsors
Radiopharm Theranostics Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 = 18 years of age. 3. Participants with a documented history of histopathologically confirmed metastatic NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, and endometrial cancer 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 tumour tissue undergo IHC testing as determined by a validated test (tumour tissue may be obtained from archived samples or from a freshly obtained biopsy). - 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 Oncology 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 hormone (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 dose 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 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. 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.
Exclusion criteria
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 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 (calculated using Cockcroft-Gault formula, or measured) < 60 mL/min - Platelet count of < 100 × 10^9/L - Absolute neutrophil count (ANC) < 1.5 × 10^9/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 normalised 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. 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 - 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% - 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. The following exclusion criteria applies to participants in Phase I: 11. Major surgery within 4 weeks prior to first dose of 177Lu-RAD204tr. 12. 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. 13. 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. 14. Has had or is scheduled to have major surgery < 28 days prior to the first dose of 177Lu-RAD204tr. 15. Positive status for human immunodeficiency virus (HIV). 16. 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. 17. Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities. 18. Any uncontrolled intercurrent illness or clinically significant uncontrolled condition(s), including but not limited to active bacterial, fungal, or viral infections requiring systemic therapy.
Outcome results
None listed