Metastatic Solid Tumors
Conditions
Keywords
metastatic solid tumors, metastatic cancer, solid tumor, positron-emission tomography, PET
Brief summary
This is a Phase 1 study evaluating the feasibility of using SLR-108 for positron-emission tomography (PET) imaging of metastatic solid tumors.
Detailed description
This study will assess the safety, pharmacokinetics, biodistribution, radiation dosimetry, and image quality of a single IV injection of the diagnostic radiopharmaceutical SLR-108, evaluating a range of antibody protein dose levels and radioactivity dose levels in subjects with metastatic solid tumors. PET imaging will be performed following administration of SLR-108.
Interventions
DRUGSLR-108
SLR-108 is an antibody-radionuclide conjugate.
DRUGSLX-1411
SLX-1411 is a non-radiolabeled antibody.
Sponsors
Solve Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
In Part 1, groups of participants will receive sequentially escalating doses of total antibody protein dose and an initial radioactivity dose. Sequential PET scans will be performed to determine the optimal antibody protein dose and scan schedule. In Part 2, a lower radioactivity dose will be evaluated in a further cohort if justified by the image quality in Part 1. The total antibody protein dose to be assessed in Part 2 will be selected based on the information collected in Part 1. In Part 3, additional subjects will be enrolled in a confirmatory expansion cohort to evaluate the optimal antibody protein dose and radioactivity dose and a single-timepoint PET schedule as determined in the previous parts of this study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women (as appropriate for cancer type) of age ≥18 years. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * Histologically or cytologically confirmed diagnosis of solid tumor as documented in medical records. * Based on the most recent tumor assessment, presence of metastatic disease that has progressed during or following previous treatment. * Presence of radiographically measurable disease (defined as the presence of ≥1 non-osseous tumor lesion that measures ≥10 mm in longest dimension \[≥15 mm in shortest dimension for lymph nodes\] and is outside of any prior radiation field). * Prior receipt of commercially available therapies that are indicated for the subject's cancer and have a demonstrated survival benefit for that indication. * Availability of tumor tissue from fresh tumor biopsy obtained by a core needle, excisional, or incisional biopsy; or punch biopsy (for cutaneous disease); or archival sample from a previous biopsy. * Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥1 week before study drug administration. * Adequate hematological profile. * Adequate coagulation profile. * Adequate hepatic profile. * Adequate renal function. * Negative viral serology or adequate therapy for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection. * For female subjects of childbearing potential, a negative serum pregnancy test. * For female subjects of childbearing potential, willingness to use a protocol recommended method of contraception from the start of the screening period until ≥6 months after study drug administration. * For male subjects who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use a protocol recommended method of contraception from the start and until ≥6 months after study drug administration and to refrain from sperm donation from the start and until ≥12 months after study drug administration. * Willingness and ability of the subject to comply with scheduled visits, the drug administration plan, protocol-specified laboratory tests, other study procedures (including any required tumor biopsy/aspirations and all radiographic studies), and study restrictions. * Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the study drug, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.
Exclusion criteria
* Malignancy involving the central nervous system unless brain metastases have been previously treated with radiotherapy, have been stable for ≥4 weeks, and do not require corticosteroids. * Presence of another cancer with disease manifestations or therapy that could adversely affect subject safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results. * Uncontrolled ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infection) at the time of study drug administration. * Significant cardiovascular event or comorbidity. * Significant screening ECG abnormalities. * Pregnancy or breastfeeding. * Any medical condition preventing PET/CT scanning, and/or inability to tolerate up to 60 minutes of PET/CT scanning per imaging session, and/or ineligibility for PET/CT scanning due to the weight limits of the scanner. * Major surgery within 4 weeks before study drug administration. * Use of a drug known to prolong the QT interval within 7 days prior to study drug administration. * Anticipated use of a strong inhibitor or inducer of cytochrome CYP3A4 or CYP1A2. * Concurrent participation in another therapeutic or imaging clinical trial. * Any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a subject's ability to provide informed consent, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Optimal antibody protein dose | Through Day 14 | The appropriate antibody dose (in mg) for optimal imaging |
| Optimal administered activity | Through Day 14 | The appropriate radioactivity dose (in mCi) for optimal imaging |
| Optimal SLR-108 PET timing | Through Day 14 | The optimal timing of PET imaging for differentiating tumor tissue from normal background tissue |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study drug administration | Through Day 0 | Duration of study drug administration (in minutes) as assessed by radiopharmacy and clinical records |
| Study drug safety | Through Day 14 | Type, frequency, severity, timing of onset, duration, and relationship to study drug of any treatment-emergent adverse events (TEAEs); laboratory abnormalities; dose-limiting toxicities (DLTs); serious adverse events (SAEs); adverse events of special interest (AESIs); or AEs leading to interruption or modification of study drug administration. |
| Supportive care profile | Through Day 14 | Number of subjects receiving supportive care and other concomitant medications |
| Study drug pharmacokinetics - Cmax | Through Day 14 | Study drug maximum plasma concentration (Cmax) |
| Study drug pharmacokinetics - AUC | Through Day 14 | Study drug area under the concentration-time curve (AUC) |
| Study drug pharmacokinetics - t1/2 | Through Day 14 | Study drug half-life (t1/2) |
| Image Quality | Through Day 14 | Image quality scores as assessed based on SLR-108 PET |
| PET tumor lesion identification | Through Day 14 | Numbers and organ locations of tumor lesions based on tumor-to-background score as assessed qualitatively on SLR-108 PET |
| CT tumor lesion identification | Through Day 14 | Numbers and organ locations of tumor lesions as assessed by concomitant CT imaging |
| Biodistribution | Through Day 14 | Whole-body radioactivity clearance as assessed by PET |
| Normal tissue radiation dosimetry | Through Day 14 | Standardized uptake values (SUVs) for normal tissues as assessed by PET |
| Tumor tissue radiation dosimetry | Through Day 14 | SUVs for tumor lesions as assessed by PET |
| Immunogenicity | Through Day 14 | Circulating anti-drug antibodies as assessed by immunoassay |
Countries
United States
Contacts
CONTACTKristina Zakurdaeva, MD, PhD
CONTACTLangdon L Miller
Outcome results
None listed