Phase 1 Study of 68Ga-R11228 and 177Lu-R11228 in Patients with Advanced Breast Cancer
Study of Investigational Imaging and Treatment in Advanced Breast Cancer
Kathy Miller, MD
Primary Investigator
Brief description of study
This is an open-label, first-in-human, multi-center Phase 1 sub-study R11228-101A of 68Ga-R11228 (imaging agent) in study participants with advanced hormone receptor positive breast cancer. It is a sub-study of R11228-101, a first-in- human Phase 1 study of two investigational products: 68Ga-R11228 and 177Lu-R11228 (therapeutic agent). The sub- study R11228-101A is designed to characterize the safety, radiation dosimetry, pharmacokinetics of 68Ga-R11228, to evaluate inter-and intra-reader agreement of 68Ga-R11228 PET image interpretations, to describe preliminary imaging efficacy of 68Ga-R11228 and to optimize dosing and imaging time point of 68Ga-R11228 prior to proceeding to evaluate the safety of 177Lu-R11228 in sub-study R11228-101B.
Detailed description of study
This is a phase 1 study of 68Ga-R11228 and 177Lu-R11228 in breast cancer to evaluate the safety of 68Ga-R11228.
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.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Breast Cancer
-
Age: 18 years - 100 years
-
Gender: All
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.
This study investigates advanced breast cancer treatment using investigational imaging and therapeutic agents. The purpose of this study is to evaluate the safety and effectiveness of these agents in patients with hormone receptor positive and HER2 negative breast cancer. The imaging agent, designed to detect cancer lesions, will be used in a PET scan to make the lesions visible.
In the study, participants will receive a single dose of the imaging agent to assess its safety and imaging capabilities. If the imaging agent shows positive uptake, participants may receive additional treatment with a therapeutic agent. The therapeutic agent is administered in multiple doses to treat cancer lesions detected by the imaging agent.
- Who can participate: Adults 18 and older with advanced hormone receptor positive and HER2 negative breast cancer can join. They must have at least one cancer lesion and meet other health criteria.
- Study details: Participants will get an investigational imaging agent to find cancer spots using a PET scan. If eligible, they may also get a therapeutic agent to treat these spots. A placebo is not used in this study.