Clinical Trial Finder

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.

- Smallest diameter of treated or untreated nodular or linear leptomeningeal metastasis >0.5 cm on MRI (Part 2 only)

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).

Arms

Experimental: 177Lu-DTPA-omburtamab

Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles.

Interventions

Biological: - radiolabeled DPTA-omburtamab

Biological, radiolabeled DPTA-omburtamab