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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 5 sites in Australia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a Phase 0/1, First-in-Human (FIH), study to evaluate safety, tolerability, biodistribution, radiation dosimetry and preliminary anti-tumour activities of 177Lu-RAD204 in participants with selected solid tumours, to identify the MTDs/ recommended doses of 177Lu-RAD204 for future exploration. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
177Lu-RAD204
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
5 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

  • 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.
  • 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 (including PD-1/PD-L1 inhibitors) or have refused 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 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.
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  • Must have at least 1 measurable target lesion according to RECIST version 1.1.
  • Eastern Cooperative Oncology 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 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.
  • 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.
  • 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.
  • 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-RAD204im,
  • 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.
  • 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.

Who cannot join

  • History of prior organ transplant.
  • 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.
  • 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.
  • Residual toxicity ≥ Grade 2 from prior anti-cancer therapy (except alopecia).
  • History of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics, 177Lu-RAD204 or any of its excipients.
  • 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 < 80 × 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 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%
  • QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 msec for females and QTcF > 450 msec for males on screening electrocardiogram (ECG) or congenital long QT syndrome.
  • Participation in any other investigational trial at the time of informed consent signature.
  • Pregnant or lactating women.
  • The following exclusion criteria applies to participants in Phase I:
  • 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.
  • 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.
  • Has had or is scheduled to have major surgery < 28 days prior to the first dose of 177Lu-RAD204tr.Surgical procedures not considered to put participants at higher risk of AEs and/or interfere with the integrity of study outcome may be allowed on a case-by-case basis in discussion with the Sponsor.
  • Positive status for human immunodeficiency virus (HIV).
  • 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.
  • 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), including but not limited to active bacterial, fungal, or viral infections requiring systemic therapy.

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Dimitris Voliotis, MD contact

+1 646 535 5017

dv@radiopharmtheranostics.com

5 sites in 1 country

Australia5 sites, 5 recruiting

  • Cancer Research SA (CRSA)

    Adelaide, South Australia, 5000

    Vineet Kwatra, MD, vkwatra@crsa.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

    Recruiting

Other trials in Australia

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, biodistribution, radiation dosimetry and preliminary anti-tumour activities of 177Lu-RAD204 in participants with selected solid tumours, to identify the MTDs/ recommended doses of 177Lu-RAD204 for future exploration.

The study will consist of a Pre-screening Period (if applicable for PD-L1 testing), a Screening Period of up to 4 weeks, followed by a Phase 0 (Imaging) Period for imaging and dosimetry to 177Lu-RAD204im and a Phase I (Treatment) Period for 177Lu-RAD204tr dose escalation.

Read the detailed description

This is a first in human, Phase 0/1, open-label study of 177Lu-RAD204 consisting of an Imaging Period with 177Lu-RAD204im (imaging dose) and a Treatment Period with 177Lu-RAD204tr (treatment dose) to determine the recommended dose(s) for future exploration of 177Lu-RAD204 in participants with PDL1+ advanced solid tumors.

Screening Period: Screening Period of up to 4 weeks. Phase 0 (Imaging Period): Low dose (10mCi) of 177Lu-RAD204 administered on Imaging Day 1 with a follow-up period of up to 2 weeks to assess imaging, safety and dosimetry. The dose may be increased, if needed, to improve image quality.

Phase 1 (treatment Period): 177Lu-RAD204tr dose escalation

  • Treatment Period with each cycle lasting 6 weeks. Extension of the planned dose intervals are possible following discussion and agreement between the Sponsor and Investigator.
  • 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.
  • Dose Limiting Toxicity (DLT) observation period for 177Lu-RAD204tr is 6 weeks following the first injection of 177Lu-RAD204tr.
  • Should an alternative treatment schedule be explored, the DLT observation period for 177Lu-RAD204tr at that dose level will be the proposed cycle duration.
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 Imaging (im) and Treatment (tr) doses

Study groups in NCT06305962
Study groupRoleWhat they receive
177Lu-RAD204ExperimentalSingle-arm, open-label study of 177Lu-RAD204 consisting of a Phase 0 Imaging Period (Im) and a Phase 1 Treatment Period (Tr).
Receives: Drug: 177Lu-RAD204

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time Activity Curves (TACs)

    Percent of the injected activity vs time for selected organs and tumors

    Measured: 72 hours

  2. Radiation dosimetry of Lu177-RAD204im

    Absorbed radiation doses of 177Lu-RAD204im in critical organs (e.g., kidneys, bone marrow)

    Measured: 72 hours

  3. Pharmacokinetics of 177Lu-RAD204im

    Half-life of 177Lu-RAD204im in blood

    Measured: 72 hours

  4. Biokinetics of 177Lu-RAD204im

    Time-integrated activity coefficients of 177Lu-RAD204im in organs and tumor lesions

    Measured: 72 hours

  5. Safety and tolerability of 177Lu-RAD204tr

    The properties, incidence, nature and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

    Measured: 6 weeks

  6. Recommended dose(s) of 177Lu-RAD204tr for future exploration

    Incidence of dose-limiting toxicities (DLTs) during the first 6 weeks following 177Lu-RAD204tr injection cycle of treatment

    Measured: 6 weeks

Secondary outcomes (4)

  1. Safety and tolerability of a single dose of 177Lu-RAD204im

    The properties, incidence, nature and severity of AEs and SAEs per Common Terminology Criteria for Adverse Events (CTCAE) v5.0

    Measured: 6 weeks

  2. Recommended dose(s) of 177Lu-RAD204im for future exploration

    Incidence of dose-limiting toxicities (DLTs) in the first 2 weeks following 177Lu-RAD204im injection

    Measured: 2 weeks

  3. Preliminary antitumor activity of 177Lu-RAD204tr

    Objective response rates (ORR) as assessed by RECIST v1.1

    Measured: Up to 30 weeks

  4. Radiation dosimetry of 177Lu-RAD204tr

    Absorbed radiation doses of 177Lu-RAD204tr in critical organs (e.g., kidneys, bone marrow)

    Measured: 72 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2024
  2. Study start3 Jun 2024
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

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)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06305962
Sponsor's protocol ID
177Lu-RAD204.2023.0001
Status last verified
Feb 2026
First submitted
22 Feb 2024
Last updated
19 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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 5 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 20 inclusion and 33 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 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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?

Time Activity Curves (TACs) (time frame: 72 hours). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06305962.

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 19 Feb 2026.

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