PDL1 Gene MutationEarly Phase 1NCT06305962
177Lu-anti-PD-L1 sdAb in Metastatic Solid Tumors
A Early Phase 1 study testing 177Lu-RAD204 in people with PDL1 Gene Mutation and Non Small Cell Lung Cancer, run by Radiopharm Theranostics, Ltd at 6 sites in Australia.
Trial summary
This is a Phase 0/1, First-in-Human (FIH), study to evaluate safety, tolerability of 177Lu-RAD204 in participants with selected solid tumors, and to determine the MTD and/or recommended dose for future exploration. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PDL1 Gene Mutation, Non Small Cell Lung Cancer, Small Cell Lung Cancer ( SCLC )
- What is being tested?
- 177Lu-RAD204
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 6 sitesAustralia
- Study dates
- 3 Jun 2024to Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult participants ≥ 18 years of age.
- Participants with a documented history of histopathologically confirmed relapsed/refractory locally advanced, inoperable or metastatic NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, endometrial cancer or any cancer that is known to be MMR deficient or MSI high 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 or have no standard of care therapy available that is likely to provide clinical benefit.
- Participants with PD-L1 positive NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, endometrial cancer or any cancer that is known to be MMR deficient or MSI high:
- If the participant tumour's PD-L1 expression status is unknown, PD-L1 positivity will be determined by IHC testing using a validated test (tumour tissue can be obtained from archived samples or from a freshly obtained biopsy).
- Must have at least 1 measurable target lesion according to RECIST version 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
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- 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 must agree to use a highly effective method of contraception
- 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.
- Participants with active brain metastases who have not received brain-directed therapy such as radiotherapy are not eligible to enroll.
- Participants must have positive lesion(s) identified by 177Lu-RAD204 imaging dose SPECT/CT.
Who cannot join
- History of prior organ transplant.
- Any other known, active malignancy, except for treated cervical intraepithelial neoplasia or non-melanoma skin cancer.
- 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
- Residual toxicity ≥ Grade 2 from prior anti-cancer therapy (except alopecia). Patients with Grade 2 or higher toxicity due to prior treatment may be allowed on a case-by-case basis in discussion with the study Sponsor.
- History of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics
- Inadequate organ functions as reflected in laboratory parameters:
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- Creatinine clearance or body surface area (BSA) adjusted estimated glomerular filtration rate (eGFR) (calculated using any clinically validated formula, preferably Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), 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 normalized 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.
- Patients requiring blood product transfusion within 4 weeks of first dose of 177Lu-RAD204tr are not eligible to participate.
- Clinically significant cardiovascular disease
- Participation in any other investigational trial
- Pregnant or lactating women.
- Received anti-cancer therapy, including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy or investigational device, within 28 days prior to the first dose of 177Lu-RAD204tr.
- 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.
- Has had or is scheduled to have major surgery < 28 days prior to the first dose of 177Lu-RAD204tr.
- Positive status for human immunodeficiency virus (HIV).
- Active or chronic hepatitis B or C.
- Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities.
- Any uncontrolled intercurrent illness or clinically significant uncontrolled condition(s).
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Australia6 sites, 5 recruiting
- Completed
Cancer Research SA (CRSA)
Adelaide, South Australia, 5000
- Not yet recruiting
Gosford Hospital
Gosford, New South Wales, 2250
Craig Kukard, craig.kukard@health.nsw.gov.au
- Recruiting
Nepean Hospital
Kingswood, New South Wales, 2747
Veronica Wong, MD, Veronica.Wong@health.nsw.gov.au
- Recruiting
GenesisCare Murdoch
Murdoch, Western Australia, 6150
Joe Cardaci, MD, Joe.Cardaci@genesiscare.com
- Recruiting
Gold Coast University Hospital
Southport, Queensland, 4215
Suzanne Allan, Suzanne.allan@health.qld.gov.au
- Recruiting
Wollongong Hospital
Wollongong, New South Wales, 2500
Daniel Brungs, MD, ISLHD-CancerClinicalTrials@health.nsw.gov.au
About this study
Official 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
This is a Phase 0/1, First-in-Human (FIH), study to evaluate safety, tolerability of 177Lu-RAD204 in participants with selected solid tumors, and to determine the MTD and/or recommended dose for future exploration.
Read the detailed description
This is a Phase 0/1, First-in-Human (FIH), study to evaluate safety and tolerability of 177Lu-RAD204 in participants with selected solid tumors, and to determine the MTD and/or recommended dose for future exploration. Biodistribution, radiation dosimetry, and preliminary anti-tumor activity of 177Lu-RAD204 will be evaluated. During the Screening Period (up to 4 weeks), participants will receive an imaging dose (low dose of 177Lu-RAD204), to assess dosimetry and to confirm the presence of lesions, prior to enrolling in the Treatment Period.
Treatment Period (Phase 1 dose escalation): 177Lu-RAD204 treatment
- Participants will receive a treatment dose every 6 weeks (a cycle).
- Participants may be treated with multiple cycles, as long as they appear to derive clinical benefit as determined by the Investigator and provided there is adequate clinical safety and organ dosimetry data.
- To improve the ratio of tumor to healthy organ distribution of 177Lu-RAD204 an excess of unlabeled RAD204 may be administered.
- Conditions
- PDL1 Gene Mutation, Non Small Cell Lung Cancer, Small Cell Lung Cancer ( SCLC ), TNBC, Triple Negative Breast Cancer, Cutaneous Melanoma, HNSCC
- Being tested
- 177Lu-RAD204
- Keywords
- PDL1 Positive, Non Small Cell Lung Cancer, Small Cell Lung Cancer (SCLC), TNBC, Triple Negative Breast Cancer, Cutaneous Melanoma, HNSCC, Endometrial cancer, Mmr Deficiency, MSI-High
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Triple Negative Breast Neoplasms, Melanoma, Squamous Cell Carcinoma of Head and Neck, Endometrial Neoplasms, Turcot syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
177Lu-RAD204Drug
177Lu-RAD204 administered at Screening and every 6 weeks at escalating doses
| Study group | Role | What they receive |
|---|---|---|
| 177Lu-RAD204 | Experimental | Escalating doses of 177 Lu-RAD204 with or without RAD204 every 6 weeks Receives: Drug: 177Lu-RAD204 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of 177Lu-RAD204
TEAEs as defined by CTCAE v5.0
Measured: 6 weeks
Recommended dose(s) of 177Lu-RAD204 for future exploration
Incidence of dose-limiting toxicities (DLTs)
Measured: 6 weeks
Secondary outcomes (3)
Preliminary antitumor activity of 177Lu-RAD204tr
Objective response rates (ORR) as assessed by RECIST v1.1
Measured: Up to 30 weeks
Radiation dosimetry of 177Lu-RAD204
Percent of injected 177Lu-RAD204 activity (%IA) vs time in selected organs and tumors
Measured: 6 weeks
Radiation dosimetry of different doses of unlabeled RAD204 on the biodistribution of 177LuRAD204
Absorbed Radiation doses in critical organs
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start3 Jun 2024
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PDL1 Gene MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radiopharm Theranostics, Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06305962
- Sponsor's protocol ID
- 177Lu-RAD204.2023.0001
- Status last verified
- Oct 2026
- First submitted
- 22 Feb 2024
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT06305962
- Acronym / sponsor ID
- 177Lu-RAD204.2023.0001
- Conditions
- PDL1 Gene Mutation, Non Small Cell Lung Cancer, Small Cell Lung Cancer ( SCLC ), TNBC, Triple Negative Breast Cancer, Cutaneous Melanoma, HNSCC
- Keywords
- PDL1 Positive, Non Small Cell Lung Cancer, Small Cell Lung Cancer (SCLC), TNBC, Triple Negative Breast Cancer, Cutaneous Melanoma, HNSCC, Endometrial cancer, Mmr Deficiency
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Radiopharm Theranostics, LtdIndustry (pharma, biotech, devices)
- Study start
- 3 Jun 2024 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 12 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 0/1, First-in-Human (FIH), study to evaluate safety, tolerability of 177Lu-RAD204 in participants with selected solid tumors, and to determine the MTD and/or recommended dose for future exploration.
Detailed description
This is a Phase 0/1, First-in-Human (FIH), study to evaluate safety and tolerability of 177Lu-RAD204 in participants with selected solid tumors, and to determine the MTD and/or recommended dose for future exploration. Biodistribution, radiation dosimetry, and preliminary anti-tumor activity of 177Lu-RAD204 will be evaluated. During the Screening Period (up to 4 weeks), participants will receive an imaging dose (low dose of 177Lu-RAD204), to assess dosimetry and to confirm the presence of lesions, prior to enrolling in the Treatment Period.
Treatment Period (Phase 1 dose escalation): 177Lu-RAD204 treatment
- Participants will receive a treatment dose every 6 weeks (a cycle).
- Participants may be treated with multiple cycles, as long as they appear to derive clinical benefit as determined by the Investigator and provided there is adequate clinical safety and organ dosimetry data.
- To improve the ratio of tumor to healthy organ distribution of 177Lu-RAD204 an excess of unlabeled RAD204 may be administered.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 177Lu-RAD204 | Experimental | Drug: 177Lu-RAD204Escalating doses of 177 Lu-RAD204 with or without RAD204 every 6 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Adult participants ≥ 18 years of age.
- Participants with a documented history of histopathologically confirmed relapsed/refractory locally advanced, inoperable or metastatic NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, endometrial cancer or any cancer that is known to be MMR deficient or MSI high 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 or have no standard of care therapy available that is likely to provide clinical benefit.
- Participants with PD-L1 positive NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, endometrial cancer or any cancer that is known to be MMR deficient or MSI high:
- Must have at least 1 measurable target lesion according to RECIST version 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Key exclusion criteria (24 listed)
- History of prior organ transplant.
- Any other known, active malignancy, except for treated cervical intraepithelial neoplasia or non-melanoma skin cancer.
- 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
- Residual toxicity ≥ Grade 2 from prior anti-cancer therapy (except alopecia). Patients with Grade 2 or higher toxicity due to prior treatment may be allowed on a case-by-case basis in discussion with the study Sponsor.
- History of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 177Lu-RAD204177Lu-RAD204 administered at Screening and every 6 weeks at escalating doses | Drug | 177Lu-RAD204 |
Primary outcome
Safety and tolerability of 177Lu-RAD204
Time frame: 6 weeks
TEAEs as defined by CTCAE v5.0
Recommended dose(s) of 177Lu-RAD204 for future exploration
Time frame: 6 weeks
Incidence of dose-limiting toxicities (DLTs)
3 secondary outcomes
Preliminary antitumor activity of 177Lu-RAD204tr
Time frame: Up to 30 weeks
Radiation dosimetry of 177Lu-RAD204
Time frame: 6 weeks
Radiation dosimetry of different doses of unlabeled RAD204 on the biodistribution of 177LuRAD204
Time frame: 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing 177Lu-RAD204 in people with PDL1 Gene Mutation and Non Small Cell Lung Cancer, run by Radiopharm Theranostics, Ltd at 6 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dimitris Voliotis, MD (+1 646 535 5017, dv@radiopharmtheranostics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of 177Lu-RAD204 (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.