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

A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors

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.

Study Overview

• Status: Withdrawn
• Conditions: Solid Tumor, Adult; Leptomeningeal Metastasis
• Intervention / Treatment: Biological: radiolabeled DPTA-omburtamab

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).

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • The Christie Hospital NHS Foundation Trust
  • Sutton, United Kingdom
    • The Royal Marsden Hospital
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • The University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 177Lu-DTPA-omburtamab; Intracerebroventricular administration of 177Lu-DTPA-omburtamab for up to five cycles.	Biological: radiolabeled DPTA-omburtamab; Biological, radiolabeled DPTA-omburtamab; Other Names: Drug: 177Lu-DTPA-omburtamab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) and serious adverse events (SAEs)	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	1 year
Incidence of AEs and SAEs	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	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absorbed radiation dose of lutetium-177 in blood and cerebrospinal fluid (CSF)	Time-activity curves of radioactivity measurements in blood and CSF will be modeled to deliver absorbed doses in blood and CSF	2 weeks
Dosimetry analysis of lutetium-177	Whole-body dosimetry by gamma camera scans and single-photon emission computed tomography (SPECT)	2 weeks
Maximum Plasma Concentration [Cmax] in CSF	Concentration of 177Lu-DTPA-omburtamab in CSF	7 weeks
Maximum Plasma Concentration [Cmax] in serum	Concentration of 177Lu-DTPA-omburtamab in serum	7 weeks
Elimination Half Life in CSF	Concentration of 177Lu-DTPA-omburtamab in CSF	7 weeks
Elimination Half Life in serum	Concentration of 177Lu-DTPA-omburtamab in serum	7 weeks
Maximum radioactivity count of lutetium-177 in blood	The time for maximum absorbed radiation dose	2 weeks
Elimination half-life of lutetium-177 radioactivity in blood	The time for eliminating half of the radioactivity in blood	2 weeks
Response	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	2 years
Investigator-assessed Duration of Response (DoR)	DoR is defined as the time from first response to LM progression	2 years
Progression-free Survival (PFS)	PFS is defined as the time from first treatment to date of LM progression or death from any cause, whichever comes first	2 years
Overall Survival (OS)	OS is defined as the time from first treatment to date of death	2 years

Collaborators and Investigators

• Sponsor: Y-mAbs Therapeutics

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 31, 2022
• Primary Completion (ANTICIPATED): December 31, 2024
• Study Completion (ANTICIPATED): December 31, 2024

Study Registration Dates

• First Submitted: March 12, 2020
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (ACTUAL): March 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 15, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Meningeal Neoplasms; Neoplasm Metastasis; Meningeal Carcinomatosis
• Other Study ID Numbers: 302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No