LIGHTBEAM-U01 Substudy 01B: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Pembrolizumab in Combination with Investigational Agents 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

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-507179-23-00

WHO UTN

U1111-1295-3472

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. Part 1 and Part 2: To determine the safety and tolerability of study interventions.
2. Part 1: To evaluate PK profile of each investigational agent.
3. Part 1 and Part 2: To evaluate ORR per Lugano response criteria by BICR for cHL and per RECIST 1.1 by investigator per solid tumor type

Secondary objectives 6

1. Part 1 and Part 2: To evaluate ORR per Lugano response criteria by investigator for cHL.
2. Part 1 and Part 2: To evaluate DCR, DOR, and PFS per Lugano response criteria by BICR for cHL and per RECIST 1.1 by investigator per solid tumor type.
3. Part 1 and Part 2: To evaluate OS by tumor type.
4. Part 2: To evaluate the PK profile of each investigational agent.
5. Part 1 and Part 2: To evaluate the development of circulating ADAs for each investigational agent.
6. Part 1 and Part 2: To assess exploratory biomarkers for cHL participants with available biopsy material.

Conditions and MedDRA coding

Hematologic Malignancies or Solid Tumors in Pediatric and Young Adults

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003063-PIP03-22, EMEA-003104-PIP02-22

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Must have 1 of the following histologically or cytologically confirmed diagnosis of Relapsed or refractory classical Hodgkin lymphoma (cHL), that may be programmed cell death 1 protein (PD-1) naïve or PD-1 exposed (eligible for Arm 1 only), advanced melanoma that may be PD-1 naïve or PD-1 exposed (eligible for Arm 2 only), solid tumors that are microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR), that may be PD-1 naïve or PD-1 exposed (eligible for Arm 2 only) or solid tumors that are tumor mutational burden-high (TMB-H), that may be PD-1 naïve or PD-1 exposed (eligible for Arm 2 only).
2. Must have recovered from all AEs from previous anticancer therapies
3. Human immunodeficiency virus (HIV)-infected participants have well controlled HIV on antiretroviral therapy (ART)

Exclusion criteria 16

1. HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
2. Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention.
3. Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
4. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
5. Received prior anticancer therapy with an anti-PD-1, anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) in combination with either an Anti- lymphocyte-activation gene 3 (LAG-3) agent or an Anti- T-cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) agent.
6. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
7. Known additional malignancy that is progressing or has required active treatment within the past 1 year.
8. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
9. Active autoimmune disease that has required systemic treatment in the past 2 years.
10. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
11. Active infection requiring systemic therapy.
12. Concurrent active Hepatitis B and Hepatitis C virus infection.
13. History of allogenic tissue/solid organ transplant.
14. Has symptoms of or is being treated for graft versus host disease (GVHD)
15. Has not adequately recovered from major surgery or have ongoing surgical complications.
16. Known tumors involving the brainstem.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Part 1: Area Under the Curve (AUC)
2. Part 1: Maximum Concentration (Cmax)
3. Part 1: Concentration in the Blood Immediately Before the Next Dose (Ctrough)
4. Part 1: Number of Participants Who Experience Dose-limiting Toxicities (DLTs)
5. Parts 1 and 2: Number of Participants Who Report at Least 1 Adverse Event (AE)
6. Parts 1 and 2 : Number of Participants Who Discontinue Study Drug Due to an AE
7. Parts 1 and 2: Objective Response Rate (ORR) per Lugano Response Criteria by Blinded Independent Central Review (BICR)
8. Parts 1 and 2: ORR per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator

Secondary endpoints 13

1. Parts 1 and 2: ORR per Lugano Response Criteria by Investigator
2. Parts 1 and 2: Disease Control Rate (DCR) per Lugano Response Criteria by BICR
3. Parts 1 and 2: DCR per RECIST 1.1 by Investigator
4. Parts 1 and 2: Duration of response (DOR) per Lugano Response Criteria by BICR
5. Parts 1 and 2: DOR per RECIST 1.1 by Investigator
6. Parts 1 and 2: Progression Free Survival (PFS) per Lugano Response Criteria by BICR
7. Parts 1 and 2: PFS per RECIST 1.1 by Investigator
8. Parts 1 and 2: Overall Survival (OS)
9. Part 2: Area Under the Curve (AUC)
10. Part 2: Maximum Concentration (Cmax)
11. Part 2: Concentration in the Blood Immediately Before the Next Dose (Ctrough)
12. Parts 1 and 2: Antidrug Antibody (ADA) Levels
13. Parts and 2: Biomarkers for Classical Hodgkin Lymphoma (cHL)

Investigational products

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

Test 5

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

Rohini Singh

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Rohini Singh

Third parties 7

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

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