Locoregionally Recurrent Hormone-receptor Positive Breast Cancer, Metastatic Hormone Receptor Positive Breast Cancer
Conditions
Keywords
Hormone Receptor Positive Breast Cancer, Endocrine resistant, Radioisotope
Brief summary
A phase 1 study of 68Ga-R11228 and 177Lu-R11228 in breast cancer.
Detailed description
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.
Interventions
DRUG68Ga-R11228
68Ga-R11228 is a gallium-labeled small molecule radioligand that is designed to localize tumor lesions
DRUG177Lu-R11228
177Lu-R11228 is a lutetium-labeled small molecule radioligand designed to treat tumor lesions
Sponsors
Radionetics Oncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events [68Ga-R11228] | Day 1 to Day 7 | Number of participants with adverse events as assessed by NCI-CTCAE v5.0, including grade |
| Incidence of Serious Adverse Events [68Ga-R11228] | Day 1 to Day 7 | Number of participants with serious adverse events |
| Incidence of adverse events [177Lu-R11228] | Day 1 to week 36 | Number of participants with adverse events as assessed by NCI-CTCAE v5.0, including grade |
| Incidence of Serious Adverse Events [177Lu-R11228] | Day 1 to week 36 | Number of participants with serious adverse events |
| Incidence of dose limiting toxicities [177Lu-R11228] | Day 1 to week 36 | Number of participants with dose limiting toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Image quality | Day 1 | 68Ga-R11228 positron emission tomography (PET) image quality as assessed by a 5-point Likert scale |
| Absorbed dose coefficients [68Ga-R11228] | Day 1 | Absorbed dose coefficients (milliGray \[mGy\]/megabecquerel \[MBq\]) in organs. |
| Standardized uptake value in tumor lesions [68Ga-R11228] | Day 1 | Standard uptake value (SUV) in tumor lesions |
| Effective whole-body dose for 68Ga-R11228 | Day 1 | Effective whole-body dose (millisievert \[mSv\]/MBq) for 68Ga-R11228 |
| Pharmacokinetic parameters of 68Ga-R11228 | Day 1 | PK parameters, including Cmax |
| Inter-reader agreement | Day 1 | Inter-reader agreement described by Fleiss' kappa coefficient |
| Intra-reader reproducibility | Day 1 | Intra-reader reproducibility described by Cohen's kappa coefficient |
| Number of study participants with at least one tumor lesion detected | Day 1 | Number of study participants with at least one tumor lesion detected by imaging with 68Ga-R11228 |
| Proportion of tumor lesions detected by imaging with 68Ga-R11228 per study participant | Day 1 | Proportion of the number of tumor lesions positive with 68Ga-11228 imaging divided by the number of tumor lesions detected with standard of care images |
| Absorbed dose coefficients [177Lu-R11228] | 7 days | Absorbed dose coefficients (milliGray \[mGy\]/megabecquerel \[MBq\]) in organs and tumor lesions for 177Lu-R11228 |
| Pharmacokinetic parameters of 177Lu-R11228 | 7 days | PK parameters, including Cmax |
| Objective response rate | 36 weeks | Number of study participants with a complete or partial response divided by the number of study participants who had at least one 177Lu-11228 dose |
| Duration of response | 36 weeks | Time from achieving partial response or complete response to progression per RECIST v1.1 or death, whichever is sooner |
| Progression free survival | 36 weeks | Time from first 177Lu-R11228 dose until progression per RECIST v1.1 or death, whichever is sooner |
| Overall survival | 36 weeks | Time from first 177Lu-R11228 dose until death from any cause |
Countries
Australia, United States
Outcome results
None listed