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

• ClinicalTrials.gov Identifier: NCT04315246
• Recruitment Status: Withdrawn
• First Posted: March 19, 2020
• Last Update Posted: July 15, 2022
• Sponsor: Y-mAbs Therapeutics
• Information provided by (Responsible Party): Y-mAbs Therapeutics

Tracking Information

• First Submitted Date: March 12, 2020
• First Posted Date: March 19, 2020
• Last Update Posted Date: July 15, 2022
• Estimated Study Start Date: August 31, 2022
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 16, 2020)

• Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 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 [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 16, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 177Lu-DTPA-Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors (Breast, NSCLC, Malignant Melanoma)
• Official Title: A Phase I/II Trial of Intracerebroventricular 177Lu DTPA Omburtamab Radioimmunotherapy for Leptomeningeal Metastasis From Solid Tumors
• 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).

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

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Patients will receive up to five cycles of intracerebroventricular 177Lu-DTPA-omburtamab. Safety and efficacy will be investigated during treatment and follow-up period.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Leptomeningeal Metastasis
• Solid Tumor, Adult

Intervention

Biological: radiolabeled DPTA-omburtamab

Biological, radiolabeled DPTA-omburtamab

Other Name: Drug: 177Lu-DTPA-omburtamab

Study Arms

Experimental: 177Lu-DTPA-omburtamab

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

Intervention: Biological: radiolabeled DPTA-omburtamab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: July 12, 2022): 0
• Original Estimated Enrollment (submitted: March 16, 2020): 63
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom, United States

Administrative Information

• NCT Number: NCT04315246
• Other Study ID Numbers: 302
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Y-mAbs Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Y-mAbs Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Y-mAbs Therapeutics
• Verification Date: July 2022