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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06395103




Registration number
NCT06395103
Ethics application status
Date submitted
1/02/2024
Date registered
1/05/2024

Titles & IDs
Public title
Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)
Scientific title
LIGHTBEAM-U01 Substudy 01A: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors
Secondary ID [1] 0 0
MK-9999-01A
Secondary ID [2] 0 0
9999-01A
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Acute Lymphoblastic Leukemia 0 0
Diffuse Large B-cell Lymphoma 0 0
Burkitt Lymphoma 0 0
Neuroblastoma 0 0
Ewing Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Zilovertamab vedotin

Experimental: Zilovertamab vedotin - Participants receive escalating doses of zilovertamab vedotin via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks).


Treatment: Other: Zilovertamab vedotin
Administered via IV infusion
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of Participants from 1 to <18 years of Age Who Experience a Dose-Limiting Toxicity (DLT)
Timepoint [1] 0 0
Up to 42 days
Primary outcome [2] 0 0
Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs)
Timepoint [2] 0 0
Up to approximately 60 months
Primary outcome [3] 0 0
Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs
Timepoint [3] 0 0
Up to approximately 60 months
Primary outcome [4] 0 0
Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs
Timepoint [4] 0 0
Up to approximately 60 months
Primary outcome [5] 0 0
Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL)
Timepoint [5] 0 0
Up to approximately 60 months
Primary outcome [6] 0 0
Part 1 and Part 2: OR for Participants with Diffuse Large B-Cell Lymphoma (DLBCL)/Burkitt Lymphoma, Neuroblastoma, and Ewing Sarcoma
Timepoint [6] 0 0
Up to approximately 60 months
Secondary outcome [1] 0 0
Part 1 and Part 2: Area Under the Curve (AUC) of Total Antibody
Timepoint [1] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [2] 0 0
Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of Total Antibody
Timepoint [2] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [3] 0 0
Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of Total Antibody
Timepoint [3] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [4] 0 0
Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Total Antibody
Timepoint [4] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [5] 0 0
Part 1 and Part 2: AUC of Antibody-Drug Conjugate (ADC)
Timepoint [5] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [6] 0 0
Part 1 and Part 2: Cmax of Antibody-Drug Conjugate (ADC)
Timepoint [6] 0 0
ose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [7] 0 0
Part 1 and Part 2: Ctrough of Antibody-Drug Conjugate (ADC)
Timepoint [7] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [8] 0 0
Part 1 and Part 2: t1/2 of Antibody-Drug Conjugate (ADC)
Timepoint [8] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [9] 0 0
Part 1 and Part 2: AUC of Monomethyl Auristatin E (MMAE)
Timepoint [9] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [10] 0 0
Part 1 and Part 2: Cmax of Monomethyl Auristatin E (MMAE)
Timepoint [10] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [11] 0 0
Part 1 and Part 2: Ctrough of Monomethyl Auristatin E (MMAE)
Timepoint [11] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [12] 0 0
Part 1 and Part 2: t1/2 of Monomethyl Auristatin E (MMAE)
Timepoint [12] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter, and at end of infusion on Day 1 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [13] 0 0
Part 2: Number of Participants Who Experience One or More Adverse Events (AEs)
Timepoint [13] 0 0
Up to approximately 60 months
Secondary outcome [14] 0 0
Part 2: Number of Participants Who Discontinue Study Treatment Due to AEs
Timepoint [14] 0 0
Up to approximately 60 months
Secondary outcome [15] 0 0
Part 2: Number of Participants Who Receive Dose Modification Due to AEs
Timepoint [15] 0 0
Up to approximately 60 months
Secondary outcome [16] 0 0
Part 1 and Part 2: Incidence of Antidrug Antibodies (ADAs) to Zilovertamab Vedotin
Timepoint [16] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter. Each cycle is 21 days. (Up to approximately 60 months)
Secondary outcome [17] 0 0
Part 1 and Part 2: Duration of Response (DOR)
Timepoint [17] 0 0
Up to approximately 60 months
Secondary outcome [18] 0 0
Part 1 and Part 2: Percentage of Participants with DLBCL/Burkitt Lymphoma Who Receive Stem Cell Transplant (SCT)
Timepoint [18] 0 0
Up to approximately 60 months
Secondary outcome [19] 0 0
Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive SCT
Timepoint [19] 0 0
Up to approximately 60 months
Secondary outcome [20] 0 0
Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive Chimeric Antigen Receptor T (CAR-T)
Timepoint [20] 0 0
Up to approximately 60 months

Eligibility
Key inclusion criteria
The main inclusion and exclusion criteria include but are not limited to the following:



* For hematological malignancies: Confirmed diagnosis of B-precursor B-ALL or DLBCL/Burkitt lymphoma according to World Health Organization (WHO) classification of neoplasms of the lymphoid tissues.
* For solid tumor malignancies: Histologically confirmed diagnosis of neuroblastoma or Ewing sarcoma.
Minimum age
6 Months
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of solid organ transplant.
* Clinically significant (ie, active) cardiovascular disease.
* Known history of liver cirrhosis.
* Ongoing Grade >1 peripheral neuropathy.
* Demyelinating form of Charcot-Marie-Tooth disease.
* Diagnosed with Down syndrome.
* Ongoing graft-versus-host disease (GVHD) of any grade or receiving systemic GVHD treatment or prophylaxis.
* History of human immunodeficiency virus (HIV) infection.
* Contraindication or hypersensitivity to any of the study intervention components.
* Received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities.
* Ongoing, chronic corticosteroid therapy (exceeding 10 mg daily of prednisone equivalent). Prednisone equivalent dosing must have been stable for at least 4 weeks before Cycle 1 Day 1 (C1D1).
* Received a strong cytochrome P450 3A4 (CYP3A4) inhibitor within 7 days or a strong CYP3A4 inducer within 14 days before the start of study intervention or expected requirement for chronic use of a strong CYP3A4 inhibitor or inducer during the study intervention period and for 30 days after the last dose of study intervention
* Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention (except for prophylactic intrathecal chemotherapy and/or cytoreductive therapy with steroids/hydroxyurea.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
* Known additional malignancy that is progressing or has required active treatment within the past 1 year.
* Active infection requiring systemic therapy.
* Known history of Hepatitis B or known active Hepatitis C virus infection.
* Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2029
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Sydney Children's Hospital-Kids Cancer Centre ( Site 1997) - Randwick
Recruitment hospital [2] 0 0
Queensland Children's Hospital-Oncology & Haematology ( Site 1996) - Brisbane
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4101 - Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Dakota
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Dakota
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
Belgium
State/province [16] 0 0
Oost-Vlaanderen
Country [17] 0 0
Brazil
State/province [17] 0 0
Parana
Country [18] 0 0
Brazil
State/province [18] 0 0
Rio Grande Do Sul
Country [19] 0 0
Brazil
State/province [19] 0 0
Sao Paulo
Country [20] 0 0
Chile
State/province [20] 0 0
Valparaiso
Country [21] 0 0
Colombia
State/province [21] 0 0
Antioquia
Country [22] 0 0
Colombia
State/province [22] 0 0
Atlantico
Country [23] 0 0
Denmark
State/province [23] 0 0
Hovedstaden
Country [24] 0 0
France
State/province [24] 0 0
Aquitaine
Country [25] 0 0
France
State/province [25] 0 0
Ile-de-France
Country [26] 0 0
France
State/province [26] 0 0
Pays-de-la-Loire
Country [27] 0 0
France
State/province [27] 0 0
Rhone-Alpes
Country [28] 0 0
Germany
State/province [28] 0 0
Nordrhein-Westfalen
Country [29] 0 0
Hungary
State/province [29] 0 0
Budapest
Country [30] 0 0
Israel
State/province [30] 0 0
Haifa
Country [31] 0 0
Israel
State/province [31] 0 0
Ramat Gan
Country [32] 0 0
Italy
State/province [32] 0 0
Lombardia
Country [33] 0 0
Italy
State/province [33] 0 0
Roma
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Netherlands
State/province [35] 0 0
Utrecht
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid, Comunidad De
Country [38] 0 0
Sweden
State/province [38] 0 0
Vastra Gotalands Lan
Country [39] 0 0
Taiwan
State/province [39] 0 0
Taipei
Country [40] 0 0
Turkey
State/province [40] 0 0
Ankara
Country [41] 0 0
Turkey
State/province [41] 0 0
Izmir
Country [42] 0 0
United Kingdom
State/province [42] 0 0
England
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London, City Of
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Cardiff

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06395103