177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors (Breast, NSCLC, Malignant Melanoma)
- Conditions
- Solid Tumor, AdultLeptomeningeal Metastasis
- Interventions
- Biological: radiolabeled DPTA-omburtamab
- Registration Number
- NCT04315246
- Lead Sponsor
- Y-mAbs Therapeutics
- Brief Summary
Adults with leptomeningeal metastasis from solid tumors will be treated with 177Lu-DTPA-omburtamab, which is a radioactive labelling of a murine monoclonal antibody targeting B7-H3.
- Detailed Description
Part 1 is a dose-escalation phase with a 3+3 sequential-group design in which patients will receive a dosimetry dose followed by maximum of five 5-week cycles of treatment doses of intracerebroventricular 177Lu-DTPA-omburtamab.
Part 2 is a cohort-expansion phase in which patients will receive a treatment at the recommended dose determined in Part 1, until confirmed LM progression, unacceptable toxicity, or for maximum of 5 cycles, whichever comes first; however, the total number of cycles will be determined based upon data from Part 1 (e.g., the dosimetry data) to minimize the risk of radiation necrosis and decreased neurological function End of treatment will take place within 5 weeks after the last cycle and thereafter the patients will be enter the follow-up period. The patients will be followed for up until one year after first dose (Part 1) and 2 years after first dose (Part 2).
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Primary ductal or lobular breast cancer, non-small cell lung cancer, or malignant melanoma
- Type I or Type II LM with a "confirmed" or "probable" diagnosis according to EANO-ESMO guidelines 2017
- Life expectancy more than 2 months, as judged by the Investigator
- ECOG Performance status 0, 1, or 2
- Acceptable hematological status and liver and kidney function
- Written informed consent obtained in accordance with local regulations
- Presence of an intracerebroventricular access device before first dosing
- Obstructive or symptomatic communicating hydrocephalus
- Progressive systemic (extra-leptomeningeal) disease
- Uncontrolled life-threatening infection
- Ventriculo-peritoneal shunts without programmable valves. Ventriculo-atrial or ventriculo-pleural shunts
- Received craniospinal irradiation (for intraparenchymal or dural metastases) or intrathecal cytotoxic anti-cancer therapy less than 3 weeks prior to first dose of 177Lu-DTPA-omburtamab
- Severe non-hematologic organ toxicity; specifically, any renal, cardiac, hepatic, pulmonary, or gastrointestinal system toxicity Grade 3 or above prior to enrolment
- Grade 4 nervous system disorder. Hearing loss or stable neurological deficits due to brain tumor are allowed
- Unacceptable coagulation function prior to first dosing defined as INR Grade 2 or above
- Female of childbearing potential, who are pregnant, breast-feeding, intend to become pregnant, or are not using highly effective contraceptive methods or male who is not using highly effective contraceptive method
- Other significant disease or condition that in the investigator's opinion would exclude the patient from the trial.
- Smallest diameter of treated or untreated nodular or linear leptomeningeal metastasis >0.5 cm on MRI (Part 2 only)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 177Lu-DTPA-omburtamab radiolabeled DPTA-omburtamab Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles.
- Primary Outcome Measures
Name Time Method Incidence of adverse events (AEs) and serious adverse events (SAEs) 1 year Safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0. The maximum tolerated dose and the recommended phase 2 dose (RP2D) will be determined in Part 1
Incidence of AEs and SAEs 2 years In Part 2, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE version 5.0, at the RP2D defined in Part 1
- Secondary Outcome Measures
Name Time Method Elimination Half Life in serum 7 weeks Concentration of 177Lu-DTPA-omburtamab in serum
Maximum radioactivity count of lutetium-177 in blood 2 weeks The time for maximum absorbed radiation dose
Dosimetry analysis of lutetium-177 2 weeks Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)
Investigator-assessed Duration of Response (DoR) 2 years DoR is defined as the time from first response to LM progression
Maximum Plasma Concentration [Cmax] in CSF 7 weeks Concentration of 177Lu-DTPA-omburtamab in CSF
Response 2 years Objective response rate (ORR) will be defined as the proportion of all evaluable patients achieving a response as the best overall response at the time of assessment
Elimination half-life of lutetium-177 radioactivity in blood 2 weeks The time for eliminating half of the radioactivity in blood
Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF) 2 weeks Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF
Maximum Plasma Concentration [Cmax] in serum 7 weeks Concentration of 177Lu-DTPA-omburtamab in serum
Elimination Half Life in CSF 7 weeks Concentration of 177Lu-DTPA-omburtamab in CSF
Overall Survival (OS) 2 years OS is defined as the time from first treatment to date of death
Progression-free Survival (PFS) 2 years PFS is defined as the time from first treatment to date of LM progression or death from any cause, whichever comes first
Trial Locations
- Locations (8)
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
The Christie Hospital NHS Foundation Trust
🇬🇧Manchester, United Kingdom
The Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
The University of Washington
🇺🇸Seattle, Washington, United States
Johns Hopkins
🇺🇸Baltimore, Maryland, United States