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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06305962




Registration number
NCT06305962
Ethics application status
Date submitted
22/02/2024
Date registered
12/03/2024

Titles & IDs
Public title
177Lu-anti-PD-L1 SdAb in Metastatic Solid Tumors
Scientific title
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
Secondary ID [1] 0 0
177Lu-RAD204.2023.0001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PDL1 Gene Mutation 0 0
Non Small Cell Lung Cancer 0 0
Small Cell Lung Cancer ( SCLC ) 0 0
TNBC, Triple Negative Breast Cancer 0 0
Cutaneous Melanoma 0 0
HNSCC 0 0
Endometrial Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 177Lu-RAD204

Experimental: 177Lu-RAD204 - Single-arm, open-label study of 177Lu-RAD204 consisting of a Phase 0 Imaging Period (Im) and a Phase 1 Treatment Period (Tr).


Treatment: Drugs: 177Lu-RAD204
177Lu-RAD204 administered at Imaging (im) and Treatment (tr) doses
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time Activity Curves (TACs)
Timepoint [1] 0 0
72 hours
Primary outcome [2] 0 0
Radiation dosimetry of Lu177-RAD204im
Timepoint [2] 0 0
72 hours
Primary outcome [3] 0 0
Pharmacokinetics of 177Lu-RAD204im
Timepoint [3] 0 0
72 hours
Primary outcome [4] 0 0
Biokinetics of 177Lu-RAD204im
Timepoint [4] 0 0
72 hours
Primary outcome [5] 0 0
Safety and tolerability of 177Lu-RAD204tr
Timepoint [5] 0 0
6 weeks
Primary outcome [6] 0 0
Recommended dose(s) of 177Lu-RAD204tr for future exploration
Timepoint [6] 0 0
6 weeks
Secondary outcome [1] 0 0
Safety and tolerability of a single dose of 177Lu-RAD204im
Timepoint [1] 0 0
6 weeks
Secondary outcome [2] 0 0
Recommended dose(s) of 177Lu-RAD204im for future exploration
Timepoint [2] 0 0
2 weeks
Secondary outcome [3] 0 0
Preliminary antitumor activity of 177Lu-RAD204tr
Timepoint [3] 0 0
Up to 30 weeks
Secondary outcome [4] 0 0
Radiation dosimetry of 177Lu-RAD204tr
Timepoint [4] 0 0
72 hours

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 × 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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 0
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/06/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2025
Actual
Sample size
Target
23
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [2] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [3] 0 0
Icon Cancer Centre North Lakes - North Lakes
Recruitment hospital [4] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [5] 0 0
Cancer Research SA (CRSA) - Adelaide
Recruitment hospital [6] 0 0
GenesisCare Murdoch - Murdoch
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
4509 - North Lakes
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
6150 - Murdoch

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Radiopharm Theranostics, Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
A/Prof Daniel Brungs, MD
Address 0 0
Country 0 0
Phone 0 0
+610242225200
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06305962