HEAT Trial (HER2 Antibody Therapy with Lutetium-177) (RAD202)

NCT 06824155

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.

Intervention / Treatment 

  • Drug: 177Lu-RAD202

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 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).

  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 ≥4 months in the opinion of the Investigator.
  7. 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.
  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). Acceptable methods of contraception are described in Section 12.3.3 of the Protocol.
  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. Acceptable methods of contraception are described in Section 12.3.3 of the Protocol.
  10. Participants with previously treated brain metastases are eligible to participate if:
    1. 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),
    2. Do not require steroids to treat associated neurological symptoms, and
    3. Participants have no history of leptomeningeal disease or spinal
  11. For Phase 1 (Treatment Period): Participants must have positive lesion(s) by 177Lu-RAD202im SPECT/CT per central review.

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