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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]

MK-9999-01A

Secondary ID [2]

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

Diffuse Large B-cell Lymphoma

Burkitt Lymphoma

Neuroblastoma

Ewing Sarcoma

Condition category

Condition code

Cancer

Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Cancer

Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Cancer

Leukaemia - Acute leukaemia

Cancer

Neuroendocrine tumour (NET)

Cancer

Children's - Other

Cancer

Leukaemia - Chronic leukaemia

Cancer

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]

Treatment: Other

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part 1: Number of Participants from 1 to <18 years of Age Who Experience a Dose-Limiting Toxicity (DLT)

Assessment method [1]

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]

Up to 42 days

Primary outcome [2]

Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs)

Assessment method [2]

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]

Up to approximately 60 months

Primary outcome [3]

Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs

Assessment method [3]

Timepoint [3]

Up to approximately 60 months

Primary outcome [4]

Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs

Assessment method [4]

Timepoint [4]

Up to approximately 60 months

Primary outcome [5]

Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Assessment method [5]

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]

Up to approximately 60 months

Primary outcome [6]

Part 1 and Part 2: OR for Participants with Diffuse Large B-Cell Lymphoma (DLBCL)/Burkitt Lymphoma, Neuroblastoma, and Ewing Sarcoma

Assessment method [6]

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]

Up to approximately 60 months

Secondary outcome [1]

Part 1 and Part 2: Area Under the Curve (AUC) of Total Antibody

Assessment method [1]

Blood samples collected at designated time points will be used to determine the AUC of total antibody.

Timepoint [1]

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]

Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of Total Antibody

Assessment method [2]

Blood samples collected at designated time points will be used to determine the Cmax of total antibody.

Timepoint [2]

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]

Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of Total Antibody

Assessment method [3]

Blood samples collected at designated time points will be used to determine the Ctrough of total antibody.

Timepoint [3]

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]

Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Total Antibody

Assessment method [4]

Blood samples collected at designated time points will be used to determine the t1/2 of total antibody.

Timepoint [4]

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]

Part 1 and Part 2: AUC of Antibody-Drug Conjugate (ADC)

Assessment method [5]

Blood samples collected at designated time points will be used to determine the AUC of ADC.

Timepoint [5]

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]

Part 1 and Part 2: Cmax of Antibody-Drug Conjugate (ADC)

Assessment method [6]

Blood samples collected at designated time points will be used to determine the Cmax of ADC.

Timepoint [6]

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]

Part 1 and Part 2: Ctrough of Antibody-Drug Conjugate (ADC)

Assessment method [7]

Blood samples collected at designated time points will be used to determine the Ctrough of ADC.

Timepoint [7]

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]

Part 1 and Part 2: t1/2 of Antibody-Drug Conjugate (ADC)

Assessment method [8]

Blood samples collected at designated time points will be used to determine the t1/2 of ADC.

Timepoint [8]

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]

Part 1 and Part 2: AUC of Monomethyl Auristatin E (MMAE)

Assessment method [9]

Blood samples collected at designated time points will be used to determine the AUC of MMAE.

Timepoint [9]

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]

Part 1 and Part 2: Cmax of Monomethyl Auristatin E (MMAE)

Assessment method [10]

Blood samples collected at designated time points will be used to determine the Cmax of MMAE.

Timepoint [10]

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]

Part 1 and Part 2: Ctrough of Monomethyl Auristatin E (MMAE)

Assessment method [11]

Blood samples collected at designated time points will be used to determine the Ctrough of MMAE.

Timepoint [11]

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]

Part 1 and Part 2: t1/2 of Monomethyl Auristatin E (MMAE)

Assessment method [12]

Blood samples collected at designated time points will be used to determine the t1/2 of MMAE.

Timepoint [12]

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]

Part 2: Number of Participants Who Experience One or More Adverse Events (AEs)

Assessment method [13]

Timepoint [13]

Up to approximately 60 months

Secondary outcome [14]

Part 2: Number of Participants Who Discontinue Study Treatment Due to AEs

Assessment method [14]

Timepoint [14]

Up to approximately 60 months

Secondary outcome [15]

Part 2: Number of Participants Who Receive Dose Modification Due to AEs

Assessment method [15]

Timepoint [15]

Up to approximately 60 months

Secondary outcome [16]

Part 1 and Part 2: Incidence of Antidrug Antibodies (ADAs) to Zilovertamab Vedotin

Assessment method [16]

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]

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]

Part 1 and Part 2: Duration of Response (DOR)

Assessment method [17]

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]

Up to approximately 60 months

Secondary outcome [18]

Part 1 and Part 2: Percentage of Participants with DLBCL/Burkitt Lymphoma Who Receive Stem Cell Transplant (SCT)

Assessment method [18]

The percentage of participants with DLBCL/Burkitt Lymphoma who go on to receive SCT will be presented.

Timepoint [18]

Up to approximately 60 months

Secondary outcome [19]

Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive SCT

Assessment method [19]

The percentage of participants with B-ALL who go on to receive SCT will be presented.

Timepoint [19]

Up to approximately 60 months

Secondary outcome [20]

Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive Chimeric Antigen Receptor T (CAR-T)

Assessment method [20]

The percentage of participants with B-ALL who go on to receive CAR-T will be presented.

Timepoint [20]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Sydney Children's Hospital-Kids Cancer Centre ( Site 1997) - Randwick

Recruitment postcode(s) [1]

2031 - Randwick

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Colorado

Country [2]

United States of America

State/province [2]

Connecticut

Country [3]

United States of America

State/province [3]

Florida

Country [4]

United States of America

State/province [4]

Iowa

Country [5]

United States of America

State/province [5]

Missouri

Country [6]

United States of America

State/province [6]

New Jersey

Country [7]

United States of America

State/province [7]

New York

Country [8]

United States of America

State/province [8]

North Dakota

Country [9]

United States of America

State/province [9]

Oregon

Country [10]

United States of America

State/province [10]

Pennsylvania

Country [11]

United States of America

State/province [11]

South Dakota

Country [12]

United States of America

State/province [12]

Texas

Country [13]

United States of America

State/province [13]

Utah

Country [14]

Belgium

State/province [14]

Oost-Vlaanderen

Country [15]

Brazil

State/province [15]

Parana

Country [16]

Brazil

State/province [16]

Rio Grande Do Sul

Country [17]

Brazil

State/province [17]

Sao Paulo

Country [18]

Chile

State/province [18]

Valparaiso

Country [19]

Denmark

State/province [19]

Hovedstaden

Country [20]

France

State/province [20]

Ile-de-France

Country [21]

France

State/province [21]

Pays-de-la-Loire

Country [22]

France

State/province [22]

Rhone-Alpes

Country [23]

Germany

State/province [23]

Nordrhein-Westfalen

Country [24]

Hungary

State/province [24]

Budapest

Country [25]

Israel

State/province [25]

Haifa

Country [26]

Israel

State/province [26]

Ramat Gan

Country [27]

Italy

State/province [27]

Lombardia

Country [28]

Italy

State/province [28]

Roma

Country [29]

Korea, Republic of

State/province [29]

Seoul

Country [30]

Netherlands

State/province [30]

Utrecht

Country [31]

Spain

State/province [31]

Barcelona

Country [32]

Spain

State/province [32]

Madrid, Comunidad De

Country [33]

Sweden

State/province [33]

Vastra Gotalands Lan

Country [34]

Taiwan

State/province [34]

Taipei

Country [35]

Turkey

State/province [35]

Ankara

Country [36]

United Kingdom

State/province [36]

England

Country [37]

United Kingdom

State/province [37]

London, City Of

Country [38]

United Kingdom

State/province [38]

Cardiff

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Merck Sharp & Dohme LLC

Country

Ethics approval

Ethics application status

Summary

Brief summary

Substudy 01A is part of a platform study. The purpose of this study is to assess the efficacy and safety of zilovertamab vedotin in pediatric participants with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL)/Burkitt lymphoma, or neuroblastoma and in pediatric and young adult participants with Ewing sarcoma.

Trial website

https://clinicaltrials.gov/study/NCT06395103

Public notes

Contacts

Principal investigator

Name

Medical Director

Address

Merck Sharp & Dohme LLC

Country

Phone

Contact person for public queries

Name

Toll Free Number

Address

Country

Phone

1-888-577-8839

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

Register a trial

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