HER2 Gene MutationEarly Phase 1RAD202NCT06824155
HEAT Trial (HER2 Antibody Therapy With Lutetium-177)
A Early Phase 1 study testing 177Lu-RAD202 in people with HER2 Gene Mutation and Advanced Solid Tumors, run by Radiopharm Theranostics, Ltd at 5 sites in Australia.
Trial summary
This is a first-in-human, Phase 0/1, open-label study of177Lu-RAD202 to determine the recommended dose(s) for future exploration of 177Lu-RAD202 in participants with HER2 expressing advanced solid tumours. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2 Gene Mutation, Advanced Solid Tumors
- What is being tested?
- 177Lu-RAD202
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesAustralia
- Study dates
- 12 Feb 2025to 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
- 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.
Show all 15Show fewer
- 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 90 days after the last dose of 177Lu-RAD202, 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 corticosteroids 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.
Who cannot join
- 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). Patients with Grade 2 or higher toxicity due to prior treatment may be allowed on a case-by-case basis in discussion with study Sponsor provided it is deemed not to put the participant at a higher risk of treatment-related toxicity or interfere with the integrity of study data, e.g., participants with endocrinopathy on stable replacement therapy
- 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
Show all 27Show fewer
- 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 participants 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)
- 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
- Uncontrolled hypertension
- Known LVEF < 50%. (LVEF may be performed either by echocardiogram or other appropriate imaging modalities such as nuclear cardiac imaging (MUGA) or MRI).
- History of uncontrolled allergic reactions and/or have hypersensitivity to anti-HER2 monoclonal antibodies, kanamycin A or aminoglycoside therapies, or other excipients that may induce hypersensitivity
- Pregnant or lactating women
- Participants who are receiving any other investigational agents
- 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-RAD202.
- Has had or is scheduled to have major surgery ≤ 28 days prior to the first dose of 177Lu-RAD202. 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.
5 sites in 1 country
Australia5 sites, 5 recruiting
- Recruiting
St Vincents Hospital, Melbourne
Fitzroy, Victoria, 3065
Melissa Moore, MD, +61 3 9231 2211, melissa.moore@svha.org.au
- Recruiting
Nepean Hospital
Kingswood, New South Wales, 2747
Veronica Wong, MD, +61 2 4734 2156, Veronica.Wong@health.nsw.gov.au
- Recruiting
Macquarie University Hospital
Macquarie Park, New South Wales, 2109
Dhanusha Sabanathan, MD, +61 2 9812 3000, dhanusha.sabanathan@mqhealth.org.au
- Recruiting
GenesisCare Murdoch
Murdoch, Western Australia, 6150
Aviral Singh, MD, +61 8 9366 1542, Aviral.Singh@genesiscare.com
- Recruiting
Wollongong Hospital
Wollongong, New South Wales, 2500
Udit Nindra, MD, +61 2 4222 5200, udit.nindra@health.nsw.gov.au
About this study
Official title: Phase 0/1 Study of the Safety and Tolerability of 177Lu-RAD202, a Lutetium-177 Radiolabeled Single Domain Antibody Against Human Epidermal Growth Factor Receptor 2 in Patients With Advanced Solid Tumours
This is a first-in-human, Phase 0/1, open-label study of177Lu-RAD202 to determine the recommended dose(s) for future exploration of 177Lu-RAD202 in participants with HER2 expressing advanced solid tumours.
Read the detailed description
This is a first-in-human, Phase 0/1, open-label study of 177Lu-RAD202 consisting of a Screening Period, a Treatment Period with 177Lu-RAD202 and a Safety and Long-Term Follow-Up Period to determine the recommended dose(s) for future exploration of 177Lu-RAD202 in participants with HER2 expressing advanced solid tumours.
Screening Period: Screening period of up to 4 weeks Phase I (Treatment Period): 177Lu-RAD202 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 adequate clinical safety and organ dosimetry data.
- DLT observation period for 177Lu-RAD202 is 6 weeks following first injection of 177Lu-RAD202.
- Should an alternative treatment schedule be explored, the DLT observation period for 177Lu-RAD202 at that dose level will be the proposed cycle duration.
Safety Follow-Up Period:
- An End of Treatment Visit performed within 7 days of the last dose of 177Lu-RAD202
- A Safety Follow-up Visit performed every 12 ± 2 weeks from the End of Treatment Visit
- Conditions
- HER2 Gene Mutation, Advanced Solid Tumors
- Being tested
- 177Lu-RAD202
- Keywords
- HER2 positive, Neoplastic disorder, Advanced solid tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
177Lu-RAD202Drug
177Lu-RAD202 administered at treatment doses
| Study group | Role | What they receive |
|---|---|---|
| 177Lu-RAD202 | Experimental | Single-arm, open-label study of 177Lu-RAD202 Receives: Drug: 177Lu-RAD202 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of 177Lu-RAD202
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
Recommended dose(s) of 177Lu-RAD202 for future exploration
Incidence of dose-limiting toxicities (DLTs) during the first 6 weeks following 177Lu-RAD202 injection cycle of treatment
Measured: 6 weeks
Secondary outcomes (5)
Preliminary antitumor activity of 177Lu-RAD202
Objective response rates (ORR) as assessed by RECIST v1.1
Measured: Up to 30 weeks
Time Activity Curves (TACs)
Percent of the injected activity vs time for selected organs and tumors
Measured: 72 hours
Radiation dosimetry of 177Lu-RAD202
Absorbed radiation doses of 177Lu-RAD202tr in critical organs (e.g., kidneys, bone marrow)
Measured: 72 hours
Pharmacokinetics of 177Lu-RAD202
Half-life of 177Lu-RAD202 in blood
Measured: 72 hours
Biokinetics of 177Lu-RAD202
Time-integrated activity coefficients of 177Lu-RAD202 in organs and tumor lesions
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2025
- Study start12 Feb 2025
- 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 HER2 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
- NCT06824155
- Sponsor's protocol ID
- RAD202.2022.0002
- Acronym
- RAD202
- Status last verified
- Sep 2026
- First submitted
- 7 Feb 2025
- Last updated
- 24 Sep 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 24 Sep 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-RAD202, a Lutetium-177 Radiolabeled Single Domain Antibody Against Human Epidermal Growth Factor Receptor 2 in Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT06824155
- Acronym / sponsor ID
- RAD202 / RAD202.2022.0002
- Conditions
- HER2 Gene Mutation, Advanced Solid Tumors
- Keywords
- HER2 positive, Neoplastic disorder, Advanced solid tumors
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Radiopharm Theranostics, LtdIndustry (pharma, biotech, devices)
- Study start
- 12 Feb 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 13 Feb 2025 (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 first-in-human, Phase 0/1, open-label study of177Lu-RAD202 to determine the recommended dose(s) for future exploration of 177Lu-RAD202 in participants with HER2 expressing advanced solid tumours.
Detailed description
This is a first-in-human, Phase 0/1, open-label study of 177Lu-RAD202 consisting of a Screening Period, a Treatment Period with 177Lu-RAD202 and a Safety and Long-Term Follow-Up Period to determine the recommended dose(s) for future exploration of 177Lu-RAD202 in participants with HER2 expressing advanced solid tumours.
Screening Period: Screening period of up to 4 weeks Phase I (Treatment Period): 177Lu-RAD202 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 adequate clinical safety and organ dosimetry data.
- DLT observation period for 177Lu-RAD202 is 6 weeks following first injection of 177Lu-RAD202.
- Should an alternative treatment schedule be explored, the DLT observation period for 177Lu-RAD202 at that dose level will be the proposed cycle duration.
Safety Follow-Up Period:
- An End of Treatment Visit performed within 7 days of the last dose of 177Lu-RAD202
- A Safety Follow-up Visit performed every 12 ± 2 weeks from the End of Treatment Visit
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 177Lu-RAD202 | Experimental | Drug: 177Lu-RAD202Single-arm, open-label study of 177Lu-RAD202 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (27 listed)
- 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). Patients with Grade 2 or higher toxicity due to prior treatment may be allowed on a case-by-case basis in discussion with study Sponsor provided it is deemed not to put the participant at a higher risk of treatment-related toxicity or interfere with the integrity of study data, e.g., participants with endocrinopathy on stable replacement therapy
- Inadequate organ functions as reflected in laboratory parameters:
- Significant cardiovascular disease including:
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-RAD202177Lu-RAD202 administered at treatment doses | Drug | 177Lu-RAD202 |
Primary outcome
Safety and tolerability of 177Lu-RAD202
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
Recommended dose(s) of 177Lu-RAD202 for future exploration
Time frame: 6 weeks
Incidence of dose-limiting toxicities (DLTs) during the first 6 weeks following 177Lu-RAD202 injection cycle of treatment
5 secondary outcomes
Preliminary antitumor activity of 177Lu-RAD202
Time frame: Up to 30 weeks
Time Activity Curves (TACs)
Time frame: 72 hours
Radiation dosimetry of 177Lu-RAD202
Time frame: 72 hours
Pharmacokinetics of 177Lu-RAD202
Time frame: 72 hours
Biokinetics of 177Lu-RAD202
Time frame: 72 hours
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 24 Sep 2026.
- Individual participant dataSharing planned: No
Related trials for HER2 Gene Mutation
RecruitingPhase 1
Whole Body HER2 Quantification With 89Zr-Trastuzumab PET/CT to Asses Zr-trastuzumab Accumulation in HER2-mutated and HER2-overexpressing Metastatic Non-small Cell Lung Cancer
Lung Cancer (NSCLC), HER2 Expression
Active, not recruitingPhase 1
Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy
Adult Solid Neoplasm, Bladder Carcinoma
RecruitingPhase 2
A Study of Pembrolizumab With Trastuzumab and Chemotherapy in People With Esophagogastric Cancer
Esophageal Cancer, Gastric Adenocarcinoma
RecruitingObservational study
Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Colorectal Cancer
Colorectal Cancer Metastatic, Brain Metastases, Adult
Active, not recruitingPhase 2
Niraparib + Dostarlimab In BRCA Mutated Breast Cancer
Stage I Breast Cancer, Stage II Breast Cancer
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.
5 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-RAD202 in people with HER2 Gene Mutation and Advanced Solid Tumors, 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 15 inclusion and 27 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 24 Sep 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?
Safety and tolerability of 177Lu-RAD202 (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 24 Sep 2026; AzTrials last refreshed its copy on 7 Nov 2026.