Phase 2b Imaging Study of RAD101 in Participants With Suspected Recurrent Brain Metastases

Inclusion Criteria

• Must be ≥ 18 years of age at the time of signing the informed consent.
• Participant has one of the following histopathologically confirmed advanced solid tumors with known history of brain metastases: lung, breast, colon, kidney, or melanoma, and with known history of brain metastases. Other primary tumor diagnoses may be approved on a case-by-case basis following discussion with the Sponsor.
• Participant has undergone SRS or SRT for their brain metastases prior to study screening with pre-planning images available for submission to the centralized imaging reader as reference.
• Participant has suspected but not confirmed recurrent brain metastases in at least 1 lesion previously treated with SRS or SRT, based on gadolinium-enhanced volumetric MRI (MRI preferred, otherwise CT) within 8 weeks prior to Day 1, with post-SRS/SRT images available for submission to the centralized imaging reader as reference. If the SoC scan was performed > 8 weeks before Day 1, discussion with the Sponsor is required to determine eligibility. In addition, each suspected lesion must meet the following criteria:
• Size must be at least 5 mm in longest diameter seen on 2 slices on the volumetric MRI analyzed at 2.5 mm slice thickness, AND
• Lesion does not meet complete response criteria or unequivocal progressive disease criteria in the medical opinion of the evaluating provider or as outlined in Appendix 5 (Section 10.5). Note: New brain metastases or new leptomeningeal disease based on macrocyclic gadolinium-enhanced MRI within 6 weeks prior to Day 1, in addition to the above findings, are permitted.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Estimated glomerular filtration rate (eGFR) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and individualized for participant's body surface area (BSA) ≥ 45 ml/min (ie, nonindexed GFR = indexed GFR × BSA (m2)/1.73 m2)
• Life expectancy ≥4 months
• Participant is not scheduled to undergo a confirmatory biopsy to characterize MRI findings until after the Day 1 study procedures have been completed.
• Female participants must meet either of the following criteria:
• Women of childbearing potential (WOCBP) must have a negative beta human chorionic gonadotropin (β-hCG) test within 72 hours before administration of IMP and must not be breastfeeding. WOCBP, defined as all women physiologically capable of becoming pregnant, should agree to use highly effective methods of contraception during dosing and for 12 hours after administration of RAD101.
• Women who are not of childbearing potential are those who are surgically sterile or post-menopausal. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
• Male participants who are able to father a child must agree to avoid impregnating a partner and to adhere to a highly effective method of contraception during dosing and for 12 hours after administration of IMP. All male participants must agree to not donate sperm for 12 hours after administration of IMP. Highly effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (i.e., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception.
• Female sterilization (have had bilateral surgical oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
• Male sterilization (at least 6 months prior to Screening). The vasectomized male partner should be the sole partner for that participant and the absence of sperm should be confirmed.
• Use of oral, injected, or implanted hormonal methods of contraception, or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that inhibit ovulation and have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking IMP. Acceptable contraception methods are further described in the protocol.
• Willing and capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF), and willing to comply with all study procedures.

Exclusion Criteria

• History of known additional malignancy that is progressing or requires treatment.
• Brain surgery for the target lesion within 4 weeks before the screening MRI.
• Whole brain Radiation Therapy (RT), SRT, or SRS within 6 weeks of Day 1
• Baseline Fridericia-corrected QT interval (QTcF) > 470 msec or history of congenital long QT syndrome
• Any medical condition that would, in the Investigator's judgment, prevent the participant's full participation in the clinical study due to safety concerns or compliance with clinical study procedures, such as participants with severe claustrophobia who are unresponsive to oral anxiolytics, participants with low back pain who cannot lie comfortably on an imaging table, and participants who are hyperactive or hyperkinetic such that they cannot tolerate lying still for multiple time point imaging procedures.
• Participation in any other investigational trial from the time of informed consent signature to the end of the Imaging and Safety Follow-Up Period if participation in the other study would interfere with the current study or would not be allowed by the other study. Participation in another study should be discussed with the Sponsor.
• History of uncontrolled allergic reactions and/or known or expected hypersensitivity to RAD101, or any of its excipients, and/or macrocyclic gadolinium-based contrast agents.