Clinical Trial Results:
A Phase I/II Dose-escalation and Expansion Cohort Trial of Intracerebroventricular Radioimmunotherapy Using 177Lu-DTPA-omburtamab in Pediatric and Adolescent Patients with Recurrent or Refractory Medulloblastoma
Summary
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EudraCT number |
2020-000670-22 |
Trial protocol |
GB DK |
Global end of trial date |
11 Aug 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Oct 2023
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First version publication date |
28 Oct 2023
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04167618 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Y-mAbs Therapeutics Inc.
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Sponsor organisation address |
230 Park Avenue, Suite 3350, New York, United States, NY 10169
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Public contact |
GRS associate, 'Y-mAbs Therapeutics Inc, +45 70261414, clinicaltrials@ymabs.com
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Scientific contact |
GRS associate, 'Y-mAbs Therapeutics Inc, +45 70261414, clinicaltrials@ymabs.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Dec 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Aug 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Aug 2022
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of Part 1 (dose-escalation phase) of this trial is to explore the tolerability of up to 2 cycles of intracerebroventricular 177Lu-DTPA-omburtamab treatment in pediatric and adolescent patients with recurrent or refractory medulloblastoma. The MTD and/or the recommended Phase 2 dose for Part 2 will be determined.
The primary objective of Part 2 (cohort-expansion phase) of this trial is to establish a safety profile of repeated dosing of 177Lu-DTPA-omburtamab in pediatric and adolescent patients with recurrent or refractory medulloblastoma.
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Protection of trial subjects |
This trial will be conducted in accordance with the protocol and with the following:
• Consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines
• Ethical considerations for clinical trials on medicinal products conducted with minors
• Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines
• Applicable laws and regulations.
The protocol, protocol amendments, patient information, ICF, investigator’s brochure, and other relevant documents (e.g., advertisements) must be submitted to an Institutional Review Board (IRB)/Ethics Committee (EC) by the investigator and reviewed and approved by the IRB/EC before the trial is initiated.
• Any amendments to the protocol will require regulatory and IRB/EC approval before implementation of changes made to the trial design, except for changes necessary to eliminate an immediate hazard to trial patients.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Sep 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 1
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Country: Number of subjects enrolled |
United States: 1
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Worldwide total number of subjects |
2
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EEA total number of subjects |
1
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
1
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Adolescents (12-17 years) |
1
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||
Pre-assignment
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Screening details |
All screening evaluations must be completed and reviewed to confirm that potential patients meet all eligibility criteria. The investigator will maintain a screening log to record details of all patients screened and to confirm eligibility or record reasons for screening failure, as applicable. | |||||||||||||||
Period 1
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Period 1 title |
Part 1 - dose escalation phase (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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10 mCi 177Lu-DTPA-omburtamab | |||||||||||||||
Arm description |
Intracerebroventricular administration of 10 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1). | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
177Lu-DTPA-omburtamab (Biological, radiolabeled DPTA-omburtamab)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intracerebroventricular use
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Dosage and administration details |
Intracerebroventricular administration of 10 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1).
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Arm title
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25 mCi 177Lu-DTPA-omburtamab | |||||||||||||||
Arm description |
Intracerebroventricular administration of 25 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1). | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
177Lu-DTPA-omburtamab (Biological, radiolabeled DPTA-omburtamab)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intracerebroventricular use
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Dosage and administration details |
Intracerebroventricular administration of 25 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1).
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Baseline characteristics reporting groups
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Reporting group title |
10 mCi 177Lu-DTPA-omburtamab
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Reporting group description |
Intracerebroventricular administration of 10 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
25 mCi 177Lu-DTPA-omburtamab
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Reporting group description |
Intracerebroventricular administration of 25 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
10 mCi 177Lu-DTPA-omburtamab
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Reporting group description |
Intracerebroventricular administration of 10 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1). | ||
Reporting group title |
25 mCi 177Lu-DTPA-omburtamab
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Reporting group description |
Intracerebroventricular administration of 25 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1). |
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End point title |
Dose Limiting Toxicities (DLTs) Part 1 [1] | |||||||||
End point description |
Summary of DLTs in DLT evaluable subjects.
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End point type |
Primary
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End point timeframe |
Days 1 through 35 in cycle 1
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: DLTs summarised |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
From 1st dose to 5 weeks after last dose, up to 10 weeks (2 cycles).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
10 mCi 177Lu-DTPA-omburtamab
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Reporting group description |
Intracerebroventricular administration of 10 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1). 177Lu-DTPA-omburtamab: Biological, radiolabeled DPTA-omburtamab | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
25 mCi 177Lu-DTPA-omburtamab
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Reporting group description |
Intracerebroventricular administration of 25 mCi 177Lu-DTPA-omburtamab for up to two cycles (Part 1). 177Lu-DTPA-omburtamab: Biological, radiolabeled DPTA-omburta | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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19 Nov 2021 |
.• Section 1.2.1 (Summary of clinical information) updated
• Table 1 replaced
• 2.2.2.1 & 2.2.2.2: Evaluation timepoints added to the endpoints
• Added: Final assessment of the eligibility criteria is done prior to first dose
• EOT visit changed to 5-6 weeks after the last dose
• Follow-up visits re-scheduled as per first dose
• Figure 1 updated
• 3.1.1.1 simplified
• Adapted description of clinical trials (Trial 03-133 and Trial 101) and the non-clinical summary
• The primary endpoint of Part 1 changed to number of DLTs and Part 2 changed to number and severity of TEAEs
• Inclusion and exclusion criteria adapted
• Follow up changed to every 13 weeks
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20 Apr 2022 |
• Allowing a longer screening period
• Adapted exclusion criterion #6
• Allowing delay in dosing due to logistic reasons
• Adapting the sentinel dosing, so that the time frame is until first treatment dose (and not the dosimetry dose).
• Removing follow-up period from Part 1
• Removing efficacy related objectives and endpoints in Part 1
• Removing the analyses of ctDNA & B7-H3 (including the applicable objectives and endpoints)
• Schedule of Assessments updated
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
The trial was terminated after 2 subjects due to a business strategy decision. At this point the maximum tolerated dose was not established. |