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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Nov 2024 → ongoing

Decision date (initial)

2024-04-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-507178-41-00

WHO UTN

U1111-1295-3459

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Dose response, Safety, Pharmacokinetic, Therapy, Efficacy

1. Part 1: To evaluate the safety and tolerability of zilovertamab vedotin monotherapy in participants from 1 to <18 years of age
2. Part 1 and Part 2: To evaluate preliminary antitumor activity of zilovertamab vedotin monotherapy per investigator assessment in participants from birth to <18 years of age for B-ALL, DLBCL/Burkitt lymphoma, and neuroblastoma, and from birth to 25 years for Ewing sarcoma

Secondary objectives 5

1. Part 1 and Part 2: To determine PK profile of zilovertamab vedotin
2. Part 2: To evaluate the safety and tolerability of zilovertamab vedotin monotherapy in participants from birth to <18 years (B-ALL, DLBCL/Burkitt lymphoma, and neuroblastoma), and from birth to 25 years for Ewing sarcoma
3. Part 1 and Part 2: To assess the immunogenicity potential of zilovertamab vedotin
4. Part 1 and Part 2: To evaluate DOR per investigator assessment by tumor type
5. Part 1 and Part 2: To evaluate the proportion of participants by tumor type who become eligible for transplant/CAR-T while on treatment with zilovertamab vedotin

Conditions and MedDRA coding

Hematologic Malignancies or Solid Tumors in Pediatric and Young Adults

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003257-PIP01-22

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 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 (As of protocol Amendment 4, in countries in the European Economic Area [EEA], the substudy will not enroll participants with hematological malignancies)
2. For solid tumor malignancies: Histologically confirmed diagnosis of neuroblastoma or Ewing sarcoma (As of protocol Amendment 4, in countries in the European Economic Area [EEA], the substudy will only enroll participants with diagnosis of Ewing sarcoma)

Exclusion criteria 19

1. Has history of solid organ transplant.
2. Has clinically significant (ie, active) cardiovascular disease.
3. Known history of liver cirrhosis.
4. Has ongoing Grade >1 peripheral neuropathy.
5. Has demyelinating form of Charcot-Marie-Tooth disease.
6. Has been diagnosed with Down syndrome.
7. Has ongoing graft-versus-host disease (GVHD) of any grade or receiving systemic GVHD treatment or prophylaxis.
8. Has history of human immunodeficiency virus (HIV) infection.
9. Has contraindication or hypersensitivity to any of the study intervention components.
10. Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities.
11. Has 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).
12. Has 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
13. Has 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.
14. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
15. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
16. Has known additional malignancy that is progressing or has required active treatment within the past 1 year.
17. Has active infection requiring systemic therapy.
18. Has known history of Hepatitis B or known active Hepatitis C virus infection.
19. Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Part 1: Number of Participants from 1 to <18 years of Age Who Experience a Dose-Limiting Toxicity (DLT)
2. Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs)
3. Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs
4. Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs
5. Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL)
6. Part 1 and Part 2: OR for Participants with Diffuse Large B-Cell Lymphoma (DLBCL)/Burkitt Lymphoma, Neuroblastoma, and Ewing Sarcoma

Secondary endpoints 20

1. Part 1 and Part 2: Area Under the Curve (AUC) of Total Antibody
2. Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of Total Antibody
3. Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of Total Antibody
4. Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Total Antibody
5. Part 1 and Part 2: AUC of Antibody-Drug Conjugate (ADC)
6. Part 1 and Part 2: Cmax of Antibody-Drug Conjugate (ADC)
7. Part 1 and Part 2: Ctrough of Antibody-Drug Conjugate (ADC)
8. Part 1 and Part 2: t1/2 of Antibody-Drug Conjugate (ADC)
9. Part 1 and Part 2: AUC of Monomethyl Auristatin E (MMAE)
10. Part 1 and Part 2: Cmax of Monomethyl Auristatin E (MMAE)
11. Part 1 and Part 2: Ctrough of Monomethyl Auristatin E (MMAE)
12. Part 1 and Part 2: t1/2 of Monomethyl Auristatin E (MMAE)
13. Part 2: Number of Participants Who Experience One or More Adverse Events (AEs)
14. Part 2: Number of Participants Who Discontinue Study Treatment Due to AEs
15. Part 2: Number of Participants Who Receive Dose Modification Due to AEs
16. Part 1 and Part 2: Incidence of Antidrug antibodies (ADAs) to Zilovertamab Vedotin
17. Part 1 and Part 2: Duration of Response (DOR)
18. Part 1 and Part 2: Percentage of Participants with DLBCL/Burkitt Lymphoma Who Receive Stem Cell Transplant (SCT)
19. Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive SCT
20. Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive Chimeric Antigen Receptor T (CAR-T)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Pallavi Pillai

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Pallavi Pillai

Third parties 7

Locations

12 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 161 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

22 submissions — initial application plus substantial / non-substantial modifications