IRB Study Number 25-250
Status Recruiting
Location Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
Description
Primary Objectives
Assess the biodistribution time-course of [111In]In-MC-760 in normal organs as a function of the mass dose administered using SPECT/CT
Determine [111In]In-MC-760 dosimetry in normal organs as a function of the mass dose administered
Estimate dosimetry for different therapeutic radioisotopes in normal organs as a function of the mass dose administered
Characterize the safety and tolerability of a single-dose of [111In]In-MC-760
Secondary Objectives
Assess blood PK of [111In]In-MC-760
Estimate blood PK of MC-760 peptide
Inclusion Criteria
Signed informed consent must be obtained prior to participation in the study.
Age ≥18 years old.
ECOG performance status ≤ 2.
Patients with documented history of either histologically or cytologically confirmed diagnosis of one of the following cancers known to express B7-H3:
a. SCLC;
b. NSCLC;
c. Prostate cancer (excluding NEPC, defined as neuroendocrine differentiation confirmed by local histology and NEPC marker expression (e.g., chromogranin, synaptophysin) confirmed by local IHC);
d. Bladder cancer;
e. Breast cancer (including TNBC);
f. Esophageal cancer;
g. HNSCC;
h. Other solid tumors with local documentation of pan B7-H3 positivity (expression in at least 20% of the tumor cells) by IHC may be approved on a case-by case basis after discussion with the Sponsor’s Medical Monitor.
- Presence of at least one contrast-enhancing lesion with a longest diameter (or short axis for nodal tumor lesions) of ≥1.5 cm on diagnostic contrast-enhanced CT or MRI as measured by the Investigator.
NOTE: Patients with at least one lesion with a longest diameter ≥1.5 cm (using an isocontour of 50% SUVmax) visible on a PET/CT scan (e.g., with 18F fluorodeoxyglucose (FDG), with prostate-specific membrane antigen (PSMA) radiotracer for prostate cancer patients or with 18F-fluoroestradiol (FES) for estrogen receptor positive breast cancer patients), acquired as part of the patient’s standard care within 28 days prior to the date of informed consent signature are also eligible.
- Patients must be able to provide adequate archival tumor biopsy tissue for central retrospective IHC analyses, with preference for the most recent available sample collected after completion of the most recent prior anticancer treatment. In case no archival tissue is available, the patient may be eligible after agreement between Investigator and the Sponsor’s Medical Monitor.
Exclusion Criteria
- Out of range laboratory values defined as:
a. eGFR <60 mL/min (<1 mL/s), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) 2021 formula for adults or measured
b. Platelets <75 x 109/L
c. ANC <1.0 x 109/L
d. Hemoglobin <9 g/dL
e. Total bilirubin >1.5 x ULN (except for patients with Gilbert’s syndrome who are excluded if total bilirubin >3x ULN) or direct bilirubin >1.5x ULN
f. ALT >3 x ULN, except for patients with tumor involvement of the liver who are excluded if ALT >5 x ULN
g. AST >3 x ULN, except for patients with tumor involvement of the liver who are excluded if AST >5 x ULN
h. Lipase >1.5 x ULN
Prolonged QTc interval > 470 ms.
Pregnant or nursing (breast feeding) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
WOCBP, defined as all women physiologically capable of becoming pregnant, unless they use highly effective methods of contraception for 14 days after the dose of [111In]In-MC-760. In addition, female patients must not donate eggs for the same time periods. Women are considered postmenopausal and not of childbearing potential if they have had over 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate [generally age from 40 to 59 years], history of vasomotor symptoms [e.g., hot flush]) in the absence of other medical justification or have had surgical bilateral oophorectomy (with or without hysterectomy), or total hysterectomy at least 6 weeks prior to enrollment on the study. In the case of oophorectomy alone, a woman is considered not of childbearing potential only when her reproductive status has been confirmed by follow-up hormone level assessment.
Highly effective contraception methods include:
a. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
b. Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an IUD or IUS, or other forms of hormonal contraception that 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 study drug.
If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF.
Sexually active males who receive [111In]In-MC-760, unless they use a condom during intercourse for 14 days after the dose of [111In]In-MC-760.
Known hypersensitivity to any of the study drugs or their excipients.
Any serious uncontrolled infection (acute or chronic), such as but not limited to those caused by bacteria, viruses, fungi, or parasites, confirmed by clinical evidence, imaging, and/or relevant positive laboratory tests (e.g., blood cultures, polymerase chain reaction (PCR) for deoxyribonucleic acid (DNA)/ribonucleic acid (RNA)).
A history of or current interstitial lung disease or pneumonitis ≥Grade 2 (CTCAE v.5.0). A patient with a prior history which completely resolved may be eligible after agreement between Investigator and the Sponsor’s Medical Monitor.
Significant illness, trauma, treatment-related toxicity, psychiatric illness, or social situation that could place the patient at undue risk during study participation, alter study outcomes, or affect patient’s ability to comply with study requirements, as determined by the Investigator.
Inability to complete the needed investigational and standard imaging examinations due to any reason (e.g., severe claustrophobia, inability to lie still for the entire imaging time, unwillingness).
Major surgery within 30 days or external beam radiotherapy within 14 days prior to ICF signature.
Prostate cancer patients with a superscan (diffuse increased skeletal radioisotope uptake with absent or faint urinary tract and soft tissue uptake as seen on the bone SPECT/CT scan with a 99mTc phosphonate radiotracer).
Start of a new systemic or localized anticancer therapy or change in dose or regimen of anticancer therapy within 28 days prior to the administration of [111In]In-MC-760. A patient receiving stable systemic or localized anticancer therapy within 28 days prior to the administration of [111In]In-MC-760 and throughout the study (i.e., until final safety follow-up call) is eligible, provided that study participation does not interfere with the patient’s anticancer therapy.
Treatment with B7-H3-targeted therapy within 5 biological half-lives prior to [111In]In-MC-760 administration.
Patients who were administered any RLT, RLI, or radioisotope within 10 physical half-lives (for that radioisotope) before the administration of [111In]In-MC-760 and throughout the study (i.e., until final safety follow-up call).
Participation in any other interventional investigational trial at the time of ICF signature. Patients involved in a previous interventional investigational study that have completed treatment and are solely under observation or in long-term follow-up are eligible.
