177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors (Breast, NSCLC, Malignant Melanoma)

Y-mAbs Therapeutics

Status and phase

Withdrawn

Phase 2

Phase 1

Conditions

Leptomeningeal Metastasis

Solid Tumor, Adult

Treatments

Biological: radiolabeled DPTA-omburtamab

Study type

Interventional

Funder types

Industry

Identifiers

NCT04315246

302

Details and patient eligibility

About

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.

Full 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).

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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)