177Lu-anti-PD-L1 sdAb in Metastatic Solid Tumors

February 17, 2026 updated by: Radiopharm Theranostics, Ltd

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 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.

  4. 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.
  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 (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.
  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-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.

  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:

  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 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.
  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%
    • 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.
  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. 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.

  12. 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.

  13. 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.
  14. Positive status for human immunodeficiency virus (HIV).
  15. 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.
  16. Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities.
  17. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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).
Drug: 177Lu-RAD204
177Lu-RAD204 administered at Imaging (im) and Treatment (tr) doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time Activity Curves (TACs)
Time Frame: 72 hours
Percent of the injected activity vs time for selected organs and tumors
72 hours
Radiation dosimetry of Lu177-RAD204im
Time Frame: 72 hours
Absorbed radiation doses of 177Lu-RAD204im in critical organs (e.g., kidneys, bone marrow)
72 hours
Pharmacokinetics of 177Lu-RAD204im
Time Frame: 72 hours
Half-life of 177Lu-RAD204im in blood
72 hours
Biokinetics of 177Lu-RAD204im
Time Frame: 72 hours
Time-integrated activity coefficients of 177Lu-RAD204im in organs and tumor lesions
72 hours
Recommended dose(s) of 177Lu-RAD204tr for future exploration
Time Frame: 6 weeks
Incidence of dose-limiting toxicities (DLTs) during the first 6 weeks following 177Lu-RAD204tr injection cycle of treatment
6 weeks
Safety and tolerability of 177Lu-RAD204tr
Time Frame: 6 weeks
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
6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of a single dose of 177Lu-RAD204im
Time Frame: 6 weeks
The properties, incidence, nature and severity of AEs and SAEs per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
6 weeks
Recommended dose(s) of 177Lu-RAD204im for future exploration
Time Frame: 2 weeks
Incidence of dose-limiting toxicities (DLTs) in the first 2 weeks following 177Lu-RAD204im injection
2 weeks
Preliminary antitumor activity of 177Lu-RAD204tr
Time Frame: Up to 30 weeks
Objective response rates (ORR) as assessed by RECIST v1.1
Up to 30 weeks
Radiation dosimetry of 177Lu-RAD204tr
Time Frame: 72 hours
Absorbed radiation doses of 177Lu-RAD204tr in critical organs (e.g., kidneys, bone marrow)
72 hours

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of agreement between 177Lu-RAD204im and standard of care imaging
Time Frame: Up to 30 weeks
Standard of care imaging may include but is not limited to 18F-FDG-PET, CT-scan and/or 99mTc-MDP-bone
Up to 30 weeks
Effect of 177Lu-RAD204im and 177Lu-RAD204tr on tumor markers
Time Frame: Up to 30 weeks
Circulating tumor DNA
Up to 30 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radiopharm Theranostics, Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 3, 2024

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

February 22, 2024

First Submitted That Met QC Criteria

March 7, 2024

First Posted (Actual)

March 12, 2024

Study Record Updates

Last Update Posted (Actual)

February 19, 2026

Last Update Submitted That Met QC Criteria

February 17, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 177Lu-RAD204.2023.0001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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