Substudy 01A: Zilovertamab Vedotin in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)

Neuroblastoma Clinical Trial

Official 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06395103
• Other study ID #: 9999-01A
• Secondary ID: MK-9999-01ALIGHT
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 4, 2024
• Est. completion date: March 31, 2029

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 elapsed 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: March 31, 2029
• Est. primary completion date: March 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 25 Years

Eligibility

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

Inclusion Criteria:

• 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.

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.

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia
• Burkitt Lymphoma
• Diffuse Large B-cell Lymphoma
• Ewing Sarcoma
• Hematologic Neoplasms
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Neuroblastoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Sarcoma, Ewing

Intervention

Biological:
• Zilovertamab vedotin
Administered via IV infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants from 1 to <18 years of Age Who Experience a Dose-Limiting Toxicity (DLT)	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.	Up to 42 days
Primary	Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs)	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.	Up to approximately 60 months
Primary	Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs	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.	Up to approximately 60 months
Primary	Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs	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.	Up to approximately 60 months
Primary	Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL)	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.	Up to approximately 60 months
Primary	Part 1 and Part 2: OR for Participants with Diffuse Large B-Cell Lymphoma (DLBCL)/Burkitt Lymphoma, Neuroblastoma, and Ewing Sarcoma	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.	Up to approximately 60 months
Secondary	Part 1 and Part 2: Area Under the Curve (AUC) of Total Antibody	Blood samples collected at designated time points will be used to determine the AUC of total antibody.	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	Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of Total Antibody	Blood samples collected at designated time points will be used to determine the Cmax of total antibody.	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	Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of Total Antibody	Blood samples collected at designated time points will be used to determine the Ctrough of total antibody.	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	Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Total Antibody	Blood samples collected at designated time points will be used to determine the t1/2 of total antibody.	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	Part 1 and Part 2: AUC of Antibody-Drug Conjugate (ADC)	Blood samples collected at designated time points will be used to determine the AUC of ADC.	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	Part 1 and Part 2: Cmax of Antibody-Drug Conjugate (ADC)	Blood samples collected at designated time points will be used to determine the Cmax of ADC.	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	Part 1 and Part 2: Ctrough of Antibody-Drug Conjugate (ADC)	Blood samples collected at designated time points will be used to determine the Ctrough of ADC.	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	Part 1 and Part 2: t1/2 of Antibody-Drug Conjugate (ADC)	Blood samples collected at designated time points will be used to determine the t1/2 of ADC.	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	Part 1 and Part 2: AUC of Monomethyl Auristatin E (MMAE)	Blood samples collected at designated time points will be used to determine the AUC of MMAE.	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	Part 1 and Part 2: Cmax of Monomethyl Auristatin E (MMAE)	Blood samples collected at designated time points will be used to determine the Cmax of MMAE.	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	Part 1 and Part 2: Ctrough of Monomethyl Auristatin E (MMAE)	Blood samples collected at designated time points will be used to determine the Ctrough of MMAE.	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	Part 1 and Part 2: t1/2 of Monomethyl Auristatin E (MMAE)	Blood samples collected at designated time points will be used to determine the t1/2 of MMAE.	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	Part 2: Number of Participants Who Experience One or More Adverse Events (AEs)	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.	Up to approximately 60 months
Secondary	Part 2: Number of Participants Who Discontinue Study Treatment Due to AEs	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.	Up to approximately 60 months
Secondary	Part 2: Number of Participants Who Receive Dose Modification Due to AEs	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.	Up to approximately 60 months
Secondary	Part 1 and Part 2: Incidence of Antidrug Antibodies (ADAs) to Zilovertamab Vedotin	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.	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	Part 1 and Part 2: Duration of Response (DOR)	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.	Up to approximately 60 months
Secondary	Part 1 and Part 2: Percentage of Participants with DLBCL/Burkitt Lymphoma Who Receive Stem Cell Transplant (SCT)	The percentage of participants with DLBCL/Burkitt Lymphoma who go on to receive SCT will be presented.	Up to approximately 60 months
Secondary	Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive SCT	The percentage of participants with B-ALL who go on to receive SCT will be presented.	Up to approximately 60 months
Secondary	Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive Chimeric Antigen Receptor T (CAR-T)	The percentage of participants with B-ALL who go on to receive CAR-T will be presented.	Up to approximately 60 months

External Links

•   Merck Clinical Trials Information