A phase 1 study of 68Ga-R11228 and 177Lu-R11228 in breast cancer.

Patients with metastatic or locoregionally recurrent ER+ and/or PR+ and HER2 negative breast cancer will be enrolled.

Part A is being conducted to test 68Ga-R11228, a new investigational product (IP) that has been designed to detect cancer lesions in the body and make them visible on a Positron Emission Tomography (PET) scan. Three dose levels of 68Ga-R11228 will be evaluated, with each patient receiving a single dose.

Part B is being conducted to test 68Ga-R11228 and additionally 177Lu-R11228, which has been designed to treat patients who have cancer lesions with positive uptake on PET scan using 68Ga-R11228. Patients who qualify for 177Lu-R11228 treatment will receive up to 6 doses over approximately 36 weeks. Multiple 177Lu-R11228 dose levels will be evaluated in Part B.

A 5-year Follow-Up Period begins once the last cycle of 177Lu-R11228 dosing is completed.

Inclusion Criteria:

Part A

• Pathologically confirmed estrogen and/or progesterone receptor (ER/PR) positive and HER2 negative locoregionally recurrent or metastatic breast cancer
• At least one target or non-target lesion per RECIST v1.1 criteria.
• Male or non-pregnant, non-lactating female subjects age ≥18 years.

Part B

• Pathologically confirmed estrogen and/or progesterone receptor (ER/PR) positive and HER2 negative locoregionally recurrent or metastatic breast cancer
• Refractory to endocrine therapy. Note: there is no limit on prior number of lines of endocrine therapy or prior treatments with CDK4/6, AKT, PI3K and/or mTOR inhibitors.
• Received or declined at least one line of chemotherapy or antibody drug conjugate in the locoregionally recurrent or metastatic setting
• Progressive disease or intolerance to last treatment.
• At least one target lesion per RECIST v1.1 criteria.
• Male or non-pregnant, non-lactating female subjects age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy of at least six months.
• Adequate bone marrow reserve, hepatic function and renal function.

Exclusion Criteria:

Part A

• Study participant has not recovered from clinically significant adverse event(s) resulting from most recent anticancer therapy/intervention.
• Known central nervous system (CNS) disease, except for those subjects with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period.
• Radiotherapy for breast cancer ≤ 28 days prior
• Received a radionuclide within a period of less than 10 physical half-lives of the administered radionuclide prior to dosing with 68Ga-R11228.
• Any condition that precludes the proper performance of imaging procedures required in this study.

Part B

• Study participant has not recovered from clinically significant adverse event(s) resulting from most recent anticancer therapy/intervention
• Treatment with anticancer therapy or with an investigational drug or device within 21 days or 5 half-lives of the agent (whichever is shorter)
• Known central nervous system (CNS) disease, except for those subjects with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period.
• Radiotherapy for breast cancer ≤ 28 days
• Prior systemic radionuclide therapeutic treatment.
• Received a radionuclide within a period of less than 10 physical half-lives of the administered radionuclide prior to dosing with 68Ga-R11228.
• Any unresolved NCI-CTCAE Version 5.0 Grade 2 or higher toxicity (except alopecia and Grade 2 platinum-therapy related neuropathy) from previous breast cancer treatment and/or from medical/surgical procedures or interventions.
• Any condition that precludes the proper performance of imaging procedures required in this study.