A Phase 1 Study of 68Ga-R11228 and 177Lu-R11228 in Breast Cancer
- Conditions
- Locoregionally Recurrent Hormone-receptor Positive Breast CancerMetastatic Hormone Receptor Positive Breast Cancer
- Interventions
- Drug: 68Ga-R11228Drug: 177Lu-R11228
- Registration Number
- NCT07121244
- Lead Sponsor
- Radionetics Oncology
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 62
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: 68Ga-R11228 Dose Optimization Portion 68Ga-R11228 68Ga-R11228 injection at pre-defined dose levels. Part B: 68Ga-R11228 Imaging and 177Lu-R11228 Dose Ranging Portion 68Ga-R11228 68Ga-R11228 injection at pre-defined dose. 177Lu-R11228 injection at pre-defined doses. Part B: 68Ga-R11228 Imaging and 177Lu-R11228 Dose Ranging Portion 177Lu-R11228 68Ga-R11228 injection at pre-defined dose. 177Lu-R11228 injection at pre-defined doses.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Pharmacokinetic parameters of 68Ga-R11228 Day 1 Amount of 68Ga-R11228 excreted in urine
Standardized uptake value in tumor lesions [68Ga-R11228] Day 1 Standard uptake value (SUV) in tumor lesions
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.
Effective whole-body dose for 68Ga-R11228 Day 1 Effective whole-body dose (millisievert \[mSv\]/MBq) for 68Ga-R11228
Inter-reader agreement Day 1 Inter-reader agreement described by Fleiss' 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
Intra-reader reproducibility Day 1 Intra-reader reproducibility described by Cohen's kappa coefficient
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 apparent volume of distribution
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