Study of 68Ga-R10602

A phase 1 imaging study of 68Ga-R10602 in hormone-receptor positive breast cancer.

There are two eligible disease populations for the study. Population 1 are patients with metastatic or locoregionally recurrent, endocrine-resistant, ER+ and/or PR+ breast cancer who have received at least one line of chemotherapy or ADC. Population 2 are patients with ER+ and HER2- locoregional or metastatic non-resectable breast adenocarcinoma with progression on at least one line of prior endocrine therapy in the adjuvant or metastatic setting and starting next line of therapy that will include tamoxifen, fulvestrant, aromatase inhibitor, or elacestrant with or without ovarian suppression. Both disease populations are eligible for both cohorts.

Cohort 1 will consist of twelve patients. Three dose levels will be evaluated, with each patient receiving a single dose, followed by imaging at five timepoints and blood dosimetry at seven timepoints.

In Cohort 2, ten patients will receive a single dose determined based on the results from Cohort 1. These patients will undergo imaging at a single timepoint, also selected based on findings from Cohort 1, and no dosimetry will be performed.

Eligibility Criteria:
Inclusion Criteria:

1. Breast Cancer Eligibility:

   * Population 1: Pathologically confirmed ER and/or PR positive, locoregionally recurrent or metastatic breast cancer that is refractory to endocrine therapy (progression on at least one line of endocrine therapy and determined by the investigator that Study Participant would not benefit from additional endocrine therapy) who have received at least one line of chemotherapy or antibody drug conjugate in the metastatic setting (recurrence within 6 months of adjuvant chemotherapy counts as one line of therapy). There is no limit on prior number of lines of endocrine therapy. Prior treatment with CDK4/6, AKT, PI3K and/or mTOR inhibitors is permitted.
   * Population 2: Pathologically confirmed ER positive and HER2 negative locoregional or metastatic breast adenocarcinoma that is not amenable to resection, with progression on at least one line of prior endocrine therapy in the adjuvant or metastatic setting and starting next line of therapy that will include tamoxifen, fulvestrant, aromatase inhibitor, or elacestrant with or without ovarian suppression. Study Participants who will receive combination therapy (with alpelisib, capiversitib, everolimus or a CDK4/6 inhibitor) as their next line of treatment must be imaged while receiving only single agent endocrine therapy, and before starting the targeted therapy. Targeted therapy can be started after imaging.
2. Male or non-pregnant, non-lactating female Study Participant age ≥18 years. Female Study Participant of child-bearing potential and male Study Participant (if sexually active) must agree to use adequate method(s) of effective contraception during their participation in the study.

   1. Medically acceptable adequate contraception for sexually active females with child-bearing potential include: 1) surgical sterilization (such as tubal ligation or hysterectomy), 2) approved hormonal contraceptives, 3) barrier method (such as condom or diaphragm) used with a spermicide, or 4) intrauterine device (IUD).
   2. Medically acceptable adequate contraception for sexually active males include: 1) surgical sterilization (such as vasectomy), 2) a condom used with a spermicide.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
4. Adequate hepatic function as defined below (within 28 days of dosing with 68Ga R10602):

   1. Serum alanine aminotransaminase (ALT)/ aspartate aminotransaminase (AST) ≤3 × upper limit of normal (ULN) or ≤5 × ULN if liver metastases are present, and
   2. Serum bilirubin: total ≤1.5 × ULN (unless due to Gilbert's syndrome or hemolysis in which case total ≤3.0 × ULN).
5. Adequate renal function as measured by creatinine clearance calculated by the Cockcroft-Gault formula (≥60 mL/minute), determined within 28 days of dosing with 68Ga-R10602.
6. Able to understand and willing to sign an informed consent form (ICF).

Exclusion Criteria:

1. Received a radionuclide within a period of less than 10 physical half-lives of the administered radionuclide prior to dosing with 68Ga-R10602.
2. Radiotherapy ≤14 days prior to dosing with 68Ga-R10602.
3. Major surgery ≤21 days prior to dosing with 68Ga-R10602 or has not recovered from adverse effects of such procedure.
4. Severe or unstable medical condition, such as congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, as well as an uncontrolled cardiac arrhythmia requiring medication (≥Grade 2, according to NCI-CTCAE Version 5.0), myocardial infarction within 6 months prior to starting Investigational Product, or any other significant or unstable concurrent cardiac illness. Note: Stable chronic atrial fibrillation is allowed.
5. History of cerebrovascular accident within 6 months or that resulted in ongoing neurologic instability.
6. Major active infection requiring antibiotics.
7. Known active human immunodeficiency virus infection or active infection with Hepatitis B or C.
8. Acute illness within 14 days prior to dosing with 68Ga-R10602 unless mild in severity, as assessed by the Investigator.
9. Any other condition that in the opinion of the Investigator would place the Study Participant at an unacceptable risk or cause the Study Participant to be unlikely to fully participate or comply with study procedures.