HEAT Trial (HER2 Antibody Therapy With Lutetium-177)

NCT06824155 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: RAD202.2022.0002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

This is a first-in-human, Phase 0/1, open-label study of177Lu-RAD202 consisting of an Imaging Period with 177Lu-RAD202im(imaging dose) and a Treatment Period with 177Lu-RAD202tr(treatment dose) to determine the recommended dose(s) for future exploration of 177Lu-RAD202 in participants with HER2 expressing advanced solid tumours.

Conditions

HER2 Gene Mutation; Advanced Solid Tumors

Keywords

HER2 positive; Neoplastic disorder; Advanced solid tumors

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-RAD202im

  Absorbed radiation doses of 177Lu-RAD202im in critical organs (e.g., kidneys, bone marrow)

  72 hours

• Safety and tolerability of a single dose of 177Lu-RAD202tr

  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-RAD202tr for future exploration

  Incidence of dose-limiting toxicities (DLTs) during the first 6 weeks following 177Lu-RAD202tr injection cycle of treatment

  6 weeks

• Pharmacokinetics of 177Lu-RAD202im

  Half-life of 177Lu-RAD202im in blood

  72 hours

• Biokinetics of 177Lu-RAD202im

  Time-integrated activity coefficients of 177Lu-RAD202im in organs and tumor lesions

  72 hours

Secondary Outcomes (4)

• Safety and tolerability of 177Lu-RAD202im

  6 weeks

• Recommended dose(s) of 177Lu-RAD202im for future exploration

  2 weeks

• Preliminary antitumor activity of 177Lu-RAD202tr

  Up to 30 weeks

• Radiation dosimetry of 177Lu-RAD202tr

  72 hours

Other Outcomes (2)

• Level of agreement between 177Lu-RAD202im and standard of care imaging

  Up to 30 weeks

• Effect of 177Lu-RAD202im and 177Lu-RAD202tr on tumor markers

  Up to 30 weeks

Study Arms (1)

177Lu-RAD202

EXPERIMENTAL

Single-arm, open-label study of 177Lu-RAD202 consisting of a Phase 0 Imaging Period (Im) and a Phase 1 Treatment Period (Tr)

Drug: 177Lu-RAD202

Interventions

177Lu-RAD202 DRUG

177Lu-RAD202 administered at Imaging (im) and Treatment (tr) doses

177Lu-RAD202

Eligibility Criteria

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

You may qualify if:

• Aged 18 years and older.
• Written, voluntary, informed consent of the participants must be obtained in compliance with institutional, regional, and federal guidelines.
• Participants with histologically or cytologically confirmed, HER2 positive or HER2-low, advanced solid tumours that are relapsed/refractory, locally advanced not amenable to curative-intent therapy, or metastatic, with documented disease progression during or after their most recent line of anti-cancer therapy. Participants must be refractory to or intolerant of standard of care therapy or have no standard of care therapy available that is likely to provide clinical benefit.
• Participant HER2 positivity is determined by local testing and is defined as a score of 3+ on immunohistochemical analysis IHC), or, defined as a score of 2+ on IHC and positive results on in situ hybridisation (ISH). HER2-low is defined as a score of 1+ on IHC analysis or a score of 2+ on IHC analysis with ISH negative. If the participant tumor's HER2 status is unknown, it may be determined in a pre-screening step whereby the participant is asked to provide written informed consent to have their tumor tissue undergo IHC testing as determined by a validated test (tumor tissue may 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.
• Participants must have a life expectancy of ≥4 months in the opinion of the Investigator.
• Women of childbearing potential (WOCBP) must have a negative serum 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.
• WOCBP must agree to use a highly effective method of contraception during the study and for 90 days after the last dose of 177Lu-RAD202. Acceptable methods of contraception are described in Section 12.3.3 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 90 days after the last dose of 177Lu-RAD202. All male participants must agree to not donate sperm during the study and at least 14 days after the last injection of 177Lu-RAD202im and/or 90 days after the last dose of 177Lu-RAD202tr, whichever occurs later. Acceptable methods of contraception are described in Section 12.3.3 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),
• Do not require steroids to treat associated neurological symptoms, and
• Participants have no history of leptomeningeal disease or spinal cord compression.
• Participants with active brain metastases untreated with brain-directed therapy such as radiotherapy, are not eligible.

You may not qualify if:

• Participants who have any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or nonmelanoma skin cancer. Participants 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 the study Sponsor, if it is determined not to put the participant at an increased risk of adverse drug effects and/or interfere with the integrity of study outcome.
• Participants who 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 previously administered therapy (except for alopecia).
• 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 x 109/L
• Absolute neutrophil count (ANC) \< 1.5 x 109/L
• Haemoglobin \< 9 g/dL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 x upper limit of normal (ULN), or \> 5 x ULN for patients with known liver metastases
• Total bilirubin \> 1.5 x ULN, except for participants with documented Gilbert's syndrome who are eligible if total bilirubin ≤ 3 x 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.
• Significant cardiovascular disease including:
• Unstable angina and/or myocardial infarction within 6 months prior to screening
• New York Heart Association Class II or greater congestive heart failure
• Clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block)

Sponsors & Collaborators

• Radiopharm Theranostics, Ltd: lead

Study Sites (5)

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

RECRUITING

Macquarie University Hospital

Macquarie Park, New South Wales, 2109, Australia

RECRUITING

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

RECRUITING

St Vincents Hospital, Melbourne

Fitzroy, Victoria, 3065, Australia

NOT YET RECRUITING

GenesisCare Murdoch

Murdoch, Western Australia, 6150, Australia

RECRUITING

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 7, 2025
• First Posted: February 13, 2025
• Study Start: February 12, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)