A Phase 1 Study of 68Ga-R11228 and 177Lu-R11228 in Breast Cancer

Phase 1 Study of 68Ga-R11228 and 177Lu-R11228 in Patients With Advanced Breast Cancer

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

Study Overview

• Status: Recruiting
• Conditions: Locoregionally Recurrent Hormone-receptor Positive Breast Cancer; Metastatic Hormone Receptor Positive Breast Cancer
• Intervention / Treatment: Drug: 68Ga-R11228; Drug: 177Lu-R11228

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.

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kristrun Stardal; Phone Number: 8582186617; Email: kstardal@radionetics.com

Study Locations

• Australia
  • Melbourne, Australia
    • Recruiting
    • Melbourne Theranostic Innovation Centre (MTIC)
    • Contact: Chistopher Marinakis; Email: cmarinakis@mtic.net.au
• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Melvin and Bren Simon Cancer Center
      • Contact: Xin Bryan; Phone Number: 317 274 5495; Email: zhongx@iu.edu
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Recruiting
      • United Theranostics
      • Contact: Amanda Huggins; Phone Number: 667-HOPENOW; Email: clinicaltrial@unithera.com
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Recruiting
      • United Theranostics Princeton
      • Contact: Amanda Huggins; Phone Number: 667-HOPENOW; Email: clinicaltrial@unithera.com
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospital Seidman Cancer Center
      • Contact: Alberto Montero; Phone Number: (216) 844-3951; Email: Alberto.Montero@UHhospitals.org
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Nathan Comeaux; Email: NIComeaux@mdanderson.org
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah - Huntsman Cancer Institute
      • Contact: Blake Nordblad; Email: blake.nordblad@hci.utah.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: 68Ga-R11228 Dose Optimization Portion; 68Ga-R11228 injection at pre-defined dose levels.	Drug: 68Ga-R11228; 68Ga-R11228 is a gallium-labeled small molecule radioligand that is designed to localize tumor lesions
Experimental: Part B: 68Ga-R11228 Imaging and 177Lu-R11228 Dose Ranging Portion; 68Ga-R11228 injection at pre-defined dose. 177Lu-R11228 injection at pre-defined doses.	Drug: 68Ga-R11228; 68Ga-R11228 is a gallium-labeled small molecule radioligand that is designed to localize tumor lesions; Drug: 177Lu-R11228; 177Lu-R11228 is a lutetium-labeled small molecule radioligand designed to treat tumor lesions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events [68Ga-R11228]	Number of participants with adverse events as assessed by NCI-CTCAE v5.0, including grade	Day 1 to Day 7
Incidence of Serious Adverse Events [68Ga-R11228]	Number of participants with serious adverse events	Day 1 to Day 7
Incidence of adverse events [177Lu-R11228]	Number of participants with adverse events as assessed by NCI-CTCAE v5.0, including grade	Day 1 to week 36
Incidence of Serious Adverse Events [177Lu-R11228]	Number of participants with serious adverse events	Day 1 to week 36
Incidence of dose limiting toxicities [177Lu-R11228]	Number of participants with dose limiting toxicities	Day 1 to week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Image quality	68Ga-R11228 positron emission tomography (PET) image quality as assessed by a 5-point Likert scale	Day 1
Absorbed dose coefficients [68Ga-R11228]	Absorbed dose coefficients (milliGray [mGy]/megabecquerel [MBq]) in organs.	Day 1
Standardized uptake value in tumor lesions [68Ga-R11228]	Standard uptake value (SUV) in tumor lesions	Day 1
Effective whole-body dose for 68Ga-R11228	Effective whole-body dose (millisievert [mSv]/MBq) for 68Ga-R11228	Day 1
Pharmacokinetic parameters of 68Ga-R11228	PK parameters, including Cmax	Day 1
Pharmacokinetic parameters of 68Ga-R11228	PK parameters, including area under the curve	Day 1
Pharmacokinetic parameters of 68Ga-R11228	PK parameters, including half-life	Day 1
Pharmacokinetic parameters of 68Ga-R11228	PK parameters, including total plasma clearance	Day 1
Pharmacokinetic parameters of 68Ga-R11228	PK parameters, including apparent volume of distribution	Day 1
Pharmacokinetic parameters of 68Ga-R11228	Amount of 68Ga-R11228 excreted in urine	Day 1
Inter-reader agreement	Inter-reader agreement described by Fleiss' kappa coefficient	Day 1
Intra-reader reproducibility	Intra-reader reproducibility described by Cohen's kappa coefficient	Day 1
Number of study participants with at least one tumor lesion detected	Number of study participants with at least one tumor lesion detected by imaging with 68Ga-R11228	Day 1
Proportion of tumor lesions detected by imaging with 68Ga-R11228 per study participant	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	Day 1
Absorbed dose coefficients [177Lu-R11228]	Absorbed dose coefficients (milliGray [mGy]/megabecquerel [MBq]) in organs and tumor lesions for 177Lu-R11228	7 days
Pharmacokinetic parameters of 177Lu-R11228	PK parameters, including Cmax	7 days
Pharmacokinetic parameters of 177Lu-R11228	PK parameters, including area under the curve	7 days
Pharmacokinetic parameters of 177Lu-R11228	PK parameters, including half-life	7 days
Pharmacokinetic parameters of 177Lu-R11228	PK parameters, including total plasma clearance	7 days
Pharmacokinetic parameters of 177Lu-R11228	PK parameters, including apparent volume of distribution	7 days
Objective response rate	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	36 weeks
Duration of response	Time from achieving partial response or complete response to progression per RECIST v1.1 or death, whichever is sooner	36 weeks
Progression free survival	Time from first 177Lu-R11228 dose until progression per RECIST v1.1 or death, whichever is sooner	36 weeks
Overall survival	Time from first 177Lu-R11228 dose until death from any cause	36 weeks

Collaborators and Investigators

• Sponsor: Radionetics Oncology

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2033

Study Registration Dates

• First Submitted: August 6, 2025
• First Submitted That Met QC Criteria: August 6, 2025
• First Posted (Actual): August 13, 2025

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Hormone Receptor Positive Breast Cancer; Endocrine resistant; Radioisotope
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: R11228-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No