Human Epidermal Growth Factor Receptor 2 (HER2) Antibody Therapy with Lutetium-177 in Patients with Advanced Solid Tumours.

ACTRN 12625000191493

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.

Intervention/Treatment

  • Drug: 177Lu-RAD204

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:
    • 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.
  11. For Phase 1 (Treatment Period): Participants must have positive lesion(s) by 177Lu-RAD202im SPECT/CT per central review.

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