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Trial registered on ANZCTR


Registration number
ACTRN12625000191493
Ethics application status
Approved
Date submitted
26/11/2024
Date registered
18/02/2025
Date last updated
18/02/2025
Date data sharing statement initially provided
18/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Human Epidermal Growth Factor Receptor 2 (HER2) Antibody Therapy with Lutetium-177 in Patients with Advanced Solid Tumours.
Scientific 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.
Secondary ID [1] 313421 0
RAD202.2022.0002
Universal Trial Number (UTN)
Trial acronym
HEAT Trial (HER2 Antibody Therapy with Lutetium-177)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumours 335792 0
Condition category
Condition code
Cancer 332366 332366 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study involves the use of investigational compound, 177Lu-RAD202 in patients with HER2 positive advanced solid tumours. There will be 2 different phases in this study whereby Phase 0 (Imaging period) using 10 mCi of 177Lu-RAD202 and Phase I (treatment period) where 2 different dose levels (30 mCi and 40mCi) of 177Lu-RAD202 will be explored.

The investigational product/IP (177Lu-RAD202) given during Phase 0 will be indicated as 177Lu-RAD202im while the IP given during Phase 1 (treatment period) will be indicated as 177Lu-RAD202tr.

For Phase 0, after undergo screening, if patient is deemed eligible, they will be taking 1 dose of 10mCi of 177Lu-RAD202im and if they tolerate the study drug after 2 weeks and show positive uptake of 177Lu-RAD202im (i.e. 177Lu-RAD204im is being taken in by the tumour cells), they can roll-over to Phase 1 where patient will receive either 30mCi (dose level 1) or 40mCi (dose level 2) of 177Lu-RAD202tr every 6 weeks with for 3 cycles. Further treatment cycle will be considered if investigator deems that patient is receiving benefit from study drug, with sponsor approval. Only patient from Phase 0 is allowed to roll over to Phase 1.

The 2 dose levels for Phase 1 have been pre-determined as 30mCi and 40mCi.
The dose escalation/ de-escalation for this study will follow a BOIN design where Cohort 1 patients will receive 30mCi for their treatment dose. DSMC (Data Safety Monitoring Committees) will determine on the opening of Cohort 2 (40mCi) after reviewing data from Cohort 1 patient.

177Lu-RAD202 will be administered as intravenous (IV) bolus injection under the supervision of the study Investigator or appropriately qualified delegate. Patient medical record will be used to monitor adherence to the intervention.

The continuous safety evaluation will be performed by sponsor, medical monitor, the investigators. A DSMB (Data Safety Monitoring Board) or equivalent committee will be established for the determination of dose escalation and monitoring of dose-limiting toxicity (DLT) for all patients who received 177Lu-RAD202.
Intervention code [1] 329987 0
Diagnosis / Prognosis
Intervention code [2] 329988 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339926 0
Phase 0
- to assess the biodistribution of 177Lu-RAD202im in selected organs and tumour lesion.
Timepoint [1] 339926 0
Day 1, Day 2, Day 3, Day 4 and Day 8 post dose of Imaging Day 1.
Primary outcome [2] 339927 0
Phase 0
- to assess the pharmacokinetics of 177Lu-RAD202im in selected organs and tumour lesion.
Timepoint [2] 339927 0
Day 1, Day 2, Day 3, Day 4 and Day 8 post dose of Imaging Day 1.
Primary outcome [3] 340371 0
Phase 0
- to assess the radiation dosimetry of 177Lu-RAD202im in selected organs and tumour lesion.
Timepoint [3] 340371 0
Day 1, Day 2, Day 3, Day 4 and Day 8 post dose of Imaging Day 1.
Secondary outcome [1] 441949 0
Phase 1
- to assess the safety and tolerability of 177Lu-RAD202tr. (Primary outcome)
Timepoint [1] 441949 0
from the start of Cycle 1 Day 1 (treatment dose) and continuous monitoring of safety parameters listed above until patient is withdrawn from treatment.
Secondary outcome [2] 441950 0
Phase 1
- to determine the recommended dose(s) of future exploration for 177Lu-RAD202. (Primary Outcome)
Timepoint [2] 441950 0
Up to 6-week post dose of Cycle 1 Day 1
Secondary outcome [3] 443887 0
Phase 0
- to assess the safety and tolerability of a single dose of 177Lu-RAD202im
Timepoint [3] 443887 0
Up to 2 week post dose of Imaging Day 1.
Secondary outcome [4] 443888 0
Phase 0:
-To confirm the recommended dose(s) of 177Lu-RAD202im for future exploration
Timepoint [4] 443888 0
Up to 2 week post dose of Imaging Day 1.
Secondary outcome [5] 443889 0
Phase 1:
To assess the preliminary anti-tumour activity of 177Lu-RAD202tr
Timepoint [5] 443889 0
Baseline, every 6 week during active treatment (8 weeks post first dose) and every 10-14 weeks following end of treatment until withdrawal of consent/ participant lost to follow-up/ study termination, death or disease progression.
Secondary outcome [6] 443890 0
Phase 1:
To assess the biodistribution of 177Lu-RAD202tr
Timepoint [6] 443890 0
Baseline, every 6 week during active treatment (8 weeks post first dose) and every 10-14 weeks following end of treatment until withdrawal of consent/ participant lost to follow-up/ study termination, death or disease progression.
Secondary outcome [7] 443891 0
Phase 1:
- to assess the pharmacokinetics of 177Lu-RAD202tr.
Timepoint [7] 443891 0
Baseline, every 6 week during active treatment (8 weeks post first dose) and every 10-14 weeks following end of treatment until withdrawal of consent/ participant lost to follow-up/ study termination, death or disease progression.
Secondary outcome [8] 443892 0
Phase 1:
- To assess the radiation dosimetry of 177Lu-RAD202tr
Timepoint [8] 443892 0
Baseline, every 6 week during active treatment (8 weeks post first dose) and every 10-14 weeks following end of treatment until withdrawal of consent/ participant lost to follow-up/ study termination, death or disease progression.
Secondary outcome [9] 444776 0
Phase 1
- to determine the recommended dose(s) of future exploration for 177Lu-RAD202. (Primary Outcome)
Timepoint [9] 444776 0
Up to 6-week post dose of Cycle 1 Day 1
Secondary outcome [10] 444787 0
Phase 1:
To assess the preliminary anti-tumour activity of 177Lu-RAD202tr
Timepoint [10] 444787 0
Baseline, every 6 week during active treatment (8 weeks post first dose) and every 10-14 weeks following end of treatment until withdrawal of consent/ participant lost to follow-up/ study termination, death or disease progression.
Secondary outcome [11] 444788 0
Phase 1:
To assess the preliminary anti-tumour activity of 177Lu-RAD202tr
Timepoint [11] 444788 0
Baseline, every 6 week during active treatment (8 weeks post first dose) and every 10-14 weeks following end of treatment until withdrawal of consent/ participant lost to follow-up/ study termination, death or disease progression.

Eligibility
Key inclusion criteria
1. Aged 18 years and older.
2. Written, voluntary, informed consent of the participants must be obtained in compliance with institutional, regional, and federal guidelines.
3. Participants with histologically or cytologically confirmed, HER2 positive advanced solid tumours 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).
4. Must have at least 1 measurable target lesion according to RECIST version 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status <= 2.
6. Participants must have a life expectancy of more than or equal to 4 months in the opinion of the investigator.
7. Women of childbearing potential (WOCBP) must have a negative serum beta-human chorionic gonadotropin (ß-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.
8. WOCBP must agree to use a highly effective method of contraception during the study and for 60 days after the last dose of 177Lu-RAD202 (60 days is approximately 10 physical half-lives of 177Lu and > 480 effective half-lives of NM-02DOTAGA).
9. 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.
10. Participants with previously treated brain metastases are eligible to participate if:
a. 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),
b. Do not require steroids to treat associated neurological symptoms, and
c. Participants have no history of leptomeningeal disease or spinal cord compression.
11. For Phase 1 (Treatment Period): Participants must have positive lesion(s) by 177Lu-RAD202im SPECT/CT per central review.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants who have any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma 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.
2. 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.
3. Residual toxicity Grade >= 2 from previously administered therapy (except for alopecia).
4.Inadequate organ functions as reflected in laboratory parameters:
• Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 60 mL/min.
• Platelet count of < 100 x 10^9/L
• Absolute neutrophil count (ANC) < 1.5 x 10^9/L
• Haemoglobin < 9 g/dL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x 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 normalised ratio (INR) <=1.5 or prothrombin time (PT) <= 1.5 x ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) <= 1.5 x 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 ntended therapeutic range of the anticoagulant.
5. 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)
• 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%
6. 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
7. Pregnant or lactating women
8. Participants who are receiving any other investigational agents

The following exclusion criteria applies to participants in Phase 1 (Treatment Period):
9. Major surgery within 4 weeks prior to first dose of 177Lu-RAD202tr. Exceptions may be approved on a case-by-case basis in discussion with 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.
10. 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-RAD202tr.
11. Has had or is scheduled to have major surgery <=28 days prior to the first dose of 177Lu-RAD202tr. Elective surgical procedures not considered to put participants at higher risk of AEs may be allowed on a case-by-case basis in discussion with the Sponsor.
12. Positive status for human immunodeficiency virus (HIV).
13. 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.
14. Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities.
15. 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Eligible patient will receive single dose of 177Lu-RAD202im in Phase 0 and if no safety concern, patient will roll-over to Phase 1 to receive 177Lu-RAD202tr (one of the 2 treatment dose levels).
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/02/2025
Actual
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 27343 0
GenesisCare - Murdoch - Murdoch
Recruitment hospital [2] 27344 0
Nepean Hospital - Kingswood
Recruitment postcode(s) [1] 43434 0
6150 - Murdoch
Recruitment postcode(s) [2] 43435 0
2747 - Kingswood

Funding & Sponsors
Funding source category [1] 317852 0
Commercial sector/Industry
Name [1] 317852 0
Radiopharm Theranostics Ltd
Country [1] 317852 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Radiopharm Theranostics Ltd
Address
Country
Australia
Secondary sponsor category [1] 320185 0
Commercial sector/Industry
Name [1] 320185 0
GenesisCare Clinical CRO
Address [1] 320185 0
Country [1] 320185 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316534 0
Bellberry Human Research Ethics Committee F
Ethics committee address [1] 316534 0
https://bellberry.com.au/
Ethics committee country [1] 316534 0
Australia
Date submitted for ethics approval [1] 316534 0
23/10/2024
Approval date [1] 316534 0
19/12/2024
Ethics approval number [1] 316534 0

Summary
Brief summary
This study is evaluating the safety and properties of 177Lu-RAD202, a single-domain antibody joined to a radioactive lutetium isotope targeting HER2-expressing solid tumours.

You may be eligible for this study if you are an adult patient with HER2 positive advanced solid tumours that is refractory to or intolerant of standard of care treatment or have no standard of care treatment available that is likely to provide clinical benefit.,

Participants will undergo a Screening Period of up to 4 weeks, followed by a Phase 0 (Imaging) Period for imaging and receiving a single injection of 177Lu-RAD202. If they are able to tolerate this and show positive uptake in the following 2 week period, they will then proceed to a Phase I (Treatment) Period where they will be assigned a gradual increase of 177Lu-RAD202 dose delivered every 6 weeks for 3 cycles. Blood sampling and imaging studies will be performed to determine how the participant is responding to 177Lu-RAD202. Additional treatment cycles (beyond 3 cycles) will be considered if participant is deemed to receive clinical benefit from 177Lu-RAD202 and approved by study Sponsor.

Findings from this study will help determine a recommended dose of 177Lu-RAD202 for future exploration
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 138190 0
Dr Aviral Singh
Address 138190 0
GenesisCare Murdoch, 100 Murdoch Drive, Murdoch WA 6150
Country 138190 0
Australia
Phone 138190 0
+61 08 93661542
Fax 138190 0
Email 138190 0
[email protected]
Contact person for public queries
Name 138191 0
Aviral Singh
Address 138191 0
GenesisCare Murdoch, 100 Murdoch Drive, Murdoch WA 6150
Country 138191 0
Australia
Phone 138191 0
+61 08 93661542
Fax 138191 0
Email 138191 0
[email protected]
Contact person for scientific queries
Name 138192 0
Dr Dimitris Voliotis
Address 138192 0
Radiopharm Theranostics Pty. Suite 1, Level 3, 62 Lygon Street Carlton South, VIC 3053
Country 138192 0
Australia
Phone 138192 0
+61 03 98245254
Fax 138192 0
Email 138192 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.