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

NCT06305962 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 177Lu-RAD204.2023.0001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief 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. 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.

Conditions

Small Cell Lung Cancer ( SCLC ); TNBC, Triple Negative Breast Cancer; HNSCC; Endometrial Cancer; Mmr Deficiency; MSI-High; PDL1 Gene Mutation; Non Small Cell Lung Cancer; Cutaneous Melanoma

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

Outcome Measures

Primary Outcomes (6)

• Time Activity Curves (TACs)

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

  72 hours

• Radiation dosimetry of Lu177-RAD204im

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

  72 hours

• Pharmacokinetics of 177Lu-RAD204im

  Half-life of 177Lu-RAD204im in blood

  72 hours

• Biokinetics of 177Lu-RAD204im

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

  72 hours

• 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

  6 weeks

• 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

  6 weeks

Secondary Outcomes (4)

• Safety and tolerability of a single dose of 177Lu-RAD204im

  6 weeks

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

  2 weeks

• Preliminary antitumor activity of 177Lu-RAD204tr

  Up to 30 weeks

• Radiation dosimetry of 177Lu-RAD204tr

  72 hours

Other Outcomes (2)

• Level of agreement between 177Lu-RAD204im and standard of care imaging

  Up to 30 weeks

• Effect of 177Lu-RAD204im and 177Lu-RAD204tr on tumor markers

  Up to 30 weeks

Study Arms (1)

177Lu-RAD204

EXPERIMENTAL

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

Interventions

177Lu-RAD204 DRUG

177Lu-RAD204 administered at Imaging (im) and Treatment (tr) doses

177Lu-RAD204

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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:
• 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:

Sponsors & Collaborators

• Radiopharm Theranostics, Ltd: lead

Study Sites (5)

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

RECRUITING

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

RECRUITING

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

RECRUITING

Cancer Research SA (CRSA)

Adelaide, South Australia, 5000, Australia

RECRUITING

GenesisCare Murdoch

Murdoch, Western Australia, 6150, Australia

RECRUITING

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

Dimitris Voliotis, MD

CONTACT

+1 646 535 5017; dv@radiopharmtheranostics.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: March 12, 2024
• Study Start: June 3, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)