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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
Date last updated
14/07/2025

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)
Assessment method [1] 0 0
Number of participants experiencing toxicities that are possibly, probably, or definitely related to study therapy; that meet pre-defined severity criteria; and result in a change in the given dose.
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)
Assessment method [2] 0 0
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who experience at least 1 AE will be presented.
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
Assessment method [3] 0 0
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who discontinue study treatment due to an AE will be presented.
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
Assessment method [4] 0 0
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who receive a dose modification due to an AE will be presented.
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)
Assessment method [5] 0 0
OR for participants with B-ALL is defined as complete response (CR) or complete response with incomplete hematologic recovery (CRi) based on investigator's assessment per Ponte-di-Legno Consortium criteria. For Part 1 and Part 2, the OR for participants with B-ALL as assessed by investigator will be presented.
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
Assessment method [6] 0 0
OR for participants with DLBCL/Burkitt lymphoma, neuroblastoma, and Ewing sarcoma is defined as complete response (CR) or partial response (PR) based on investigator's assessment per International Pediatric Non-Hodgkin Lymphoma (IPNHL) Response Criteria for participants with DLBCL/Burkitt lymphoma, per International Neuroblastoma Response Criteria (INRC) for neuroblastoma, and per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for Ewing sarcoma. For Part 1 and Part 2, the OR for participants with DLBCL/Burkitt lymphoma, neuroblastoma, and Ewing sarcoma as assessed by investigator will be presented.
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
Assessment method [1] 0 0
Blood samples collected at designated time points will be used to determine the 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
Assessment method [2] 0 0
Blood samples collected at designated time points will be used to determine the 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
Assessment method [3] 0 0
Blood samples collected at designated time points will be used to determine the 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
Assessment method [4] 0 0
Blood samples collected at designated time points will be used to determine the 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)
Assessment method [5] 0 0
Blood samples collected at designated time points will be used to determine the AUC of 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)
Assessment method [6] 0 0
Blood samples collected at designated time points will be used to determine the Cmax of 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)
Assessment method [7] 0 0
Blood samples collected at designated time points will be used to determine the Ctrough of 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)
Assessment method [8] 0 0
Blood samples collected at designated time points will be used to determine the t1/2 of 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)
Assessment method [9] 0 0
Blood samples collected at designated time points will be used to determine the AUC of 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)
Assessment method [10] 0 0
Blood samples collected at designated time points will be used to determine the Cmax of 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)
Assessment method [11] 0 0
Blood samples collected at designated time points will be used to determine the Ctrough of 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)
Assessment method [12] 0 0
Blood samples collected at designated time points will be used to determine the t1/2 of 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)
Assessment method [13] 0 0
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 2 who experience at least 1 AE will be presented.
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
Assessment method [14] 0 0
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 2 who discontinue study treatment due to an AE will be presented.
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
Assessment method [15] 0 0
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants in Part 2 who receive a dose modification due to an AE will be presented.
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
Assessment method [16] 0 0
Blood samples collected at designated timepoints will be used to determine the ADA response to zilovertamab vedotin. The incidence of ADAs over time will be presented.
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)
Assessment method [17] 0 0
DOR is defined as the time from the first documented evidence of CR/CRi for B-ALL or CR/PR for DLBCL/Burkitt lymphoma, Ewing sarcoma, and neuroblastoma until disease progression or death due to any cause, whichever occurs first. For participants under 1-year of age, the time from the first dose will start from the first dose a participant receives during Part 2.
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)
Assessment method [18] 0 0
The percentage of participants with DLBCL/Burkitt Lymphoma who go on to receive SCT will be presented.
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
Assessment method [19] 0 0
The percentage of participants with B-ALL who go on to receive SCT will be presented.
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)
Assessment method [20] 0 0
The percentage of participants with B-ALL who go on to receive CAR-T will be presented.
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
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Dakota
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
South Dakota
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
Belgium
State/province [17] 0 0
Oost-Vlaanderen
Country [18] 0 0
Brazil
State/province [18] 0 0
Parana
Country [19] 0 0
Brazil
State/province [19] 0 0
Rio Grande Do Sul
Country [20] 0 0
Brazil
State/province [20] 0 0
Sao Paulo
Country [21] 0 0
Chile
State/province [21] 0 0
Valparaiso
Country [22] 0 0
Colombia
State/province [22] 0 0
Antioquia
Country [23] 0 0
Colombia
State/province [23] 0 0
Atlantico
Country [24] 0 0
Colombia
State/province [24] 0 0
Cordoba
Country [25] 0 0
Denmark
State/province [25] 0 0
Hovedstaden
Country [26] 0 0
France
State/province [26] 0 0
Aquitaine
Country [27] 0 0
France
State/province [27] 0 0
Ile-de-France
Country [28] 0 0
France
State/province [28] 0 0
Pays-de-la-Loire
Country [29] 0 0
France
State/province [29] 0 0
Provence-Alpes-Cote-d Azur
Country [30] 0 0
France
State/province [30] 0 0
Rhone-Alpes
Country [31] 0 0
Germany
State/province [31] 0 0
Nordrhein-Westfalen
Country [32] 0 0
Greece
State/province [32] 0 0
Attiki
Country [33] 0 0
Hungary
State/province [33] 0 0
Budapest
Country [34] 0 0
Israel
State/province [34] 0 0
Haifa
Country [35] 0 0
Israel
State/province [35] 0 0
Ramat Gan
Country [36] 0 0
Italy
State/province [36] 0 0
Lombardia
Country [37] 0 0
Italy
State/province [37] 0 0
Roma
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seoul
Country [39] 0 0
Netherlands
State/province [39] 0 0
Utrecht
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid, Comunidad De
Country [42] 0 0
Sweden
State/province [42] 0 0
Vastra Gotalands Lan
Country [43] 0 0
Taiwan
State/province [43] 0 0
Taipei
Country [44] 0 0
Turkey
State/province [44] 0 0
Ankara
Country [45] 0 0
Turkey
State/province [45] 0 0
Izmir
Country [46] 0 0
United Kingdom
State/province [46] 0 0
England
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London, City Of
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Surrey
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Cardiff

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 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
Email 0 0
Trialsites@msd.com
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