Clinical trial NCT06395090: A Study of Pembrolizumab in Combination With Investigational Agents in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01B/LIGHTBEAM-U01)
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Neoplasm Metastasis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-05-01
Enrollment: 0
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a rolling arm study of pembrolizumab in combination with investigational agents in pediatric participants with relapsed or refractory classical Hodgkin lymphoma (cHL) solid tumors with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) or tumor mutational burden-high (TMB-H). This study will have 2 parts: a safety lead-in to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D) (Part 1) followed by an efficacy evaluation (Part 2). Participants will be assigned to a treatment arm (either Part 1 or Part 2) that is open for enrollment.

There will be no hypothesis testing in this study.

Detailed description: The master screening protocol is MK-9999-U01.

Eligibility criteria: Inclusion Criteria:

* Must have 1 of the following histologically or cytologically confirmed diagnosis of Relapsed or refractory classical Hodgkin lymphoma (cHL) solid tumors that are microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR), or solid tumors that are tumor mutational burden-high (TMB-H)
* Must have recovered from all AEs from previous anticancer therapies
* Human immunodeficiency virus (HIV)-infected participants have well controlled HIV on antiretroviral therapy (ART)

Exclusion Criteria:

* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
* Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* 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
* 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
* Known additional malignancy that is progressing or has required active treatment within the past 1 year
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Active autoimmune disease that has required systemic treatment in the past 2 years
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Active infection requiring systemic therapy
* Concurrent active Hepatitis B and Hepatitis C virus infection
* History of allogenic tissue/solid organ transplant
* Has symptoms of or is being treated for graft versus host disease (GVHD)
* Has not adequately recovered from major surgery or have ongoing surgical complications
* Known tumors involving the brainstem

Primary outcomes:
measure: Part 1: Number of Participants Who Experience Dose-limiting Toxicities (DLTs)
timeFrame: Up to 21 days
measure: Parts 1 and 2: Number of Participants Who Report at Least 1 Adverse Event (AE)
timeFrame: Up to approximately 27 months
measure: Parts 1 and 2 : Number of Participants Who Discontinue Study Drug Due to an AE
timeFrame: Up to approximately 24 months
measure: Part 1: Area Under the Curve (AUC)
timeFrame: Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
measure: Part 1: Maximum Concentration (Cmax)
timeFrame: Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
measure: Part 1: Concentration in the Blood Immediately Before the Next Dose (Ctrough)
timeFrame: Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
measure: Parts 1 and 2: Objective Response Rate (ORR) per Lugano Response Criteria by Blinded Independent Central Review (BICR)
timeFrame: Up to approximately 57 months
measure: Parts 1 and 2: ORR per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator
timeFrame: Up to approximately 57 months
Secondary outcomes:
measure: Parts 1 and 2: ORR per Lugano Response Criteria by Investigator
timeFrame: Up to approximately 57 months
measure: Parts 1 and 2: Disease Control Rate (DCR) per Lugano Response Criteria by BICR
timeFrame: Up to approximately 57 months
measure: Parts 1 and 2: DCR per RECIST 1.1 by Investigator
timeFrame: Up to approximately 57 months
measure: Parts 1 and 2: Duration of Response (DOR) per Lugano Response Criteria by BICR
timeFrame: Up to approximately 57 months
measure: Parts 1 and 2: DOR per RECIST 1.1 by Investigator
timeFrame: Up to approximately 57 months
measure: Parts 1 and 2: Progression Free Survival (PFS) per Lugano Response Criteria by BICR
timeFrame: Up to approximately 57 months
measure: Parts 1 and 2: PFS per RECIST 1.1 by Investigator
timeFrame: Up to approximately 57 months
measure: Parts 1 and 2: Overall Survival (OS)
timeFrame: Up to approximately 57 months
measure: Part 2: Area Under the Curve (AUC)
timeFrame: Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
measure: Part 2: Maximum Concentration (Cmax)
timeFrame: Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
measure: Part 2: Concentration in the Blood Immediately Before the Next Dose (Ctrough)
timeFrame: Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
measure: Parts 1 and 2: Antidrug Antibody (ADA) Levels
timeFrame: Cycle 1, 2, 4, and 5: predose; once every four cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
measure: Parts 1 and 2: Biomarker Levels for Classical Hodgkin Lymphoma (cHL)
timeFrame: Up to approximately 57 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale-New Haven Hospital ( Site 2012)
state: Connecticut
city: Iowa City
country: United States
facility: University of Iowa-Holden Comprehensive Cancer Center ( Site 2017)
state: Iowa
city: Kansas City
country: United States
facility: Children's Mercy Hospital ( Site 2024)
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 2008)
state: New Jersey
city: Valhalla
country: United States
facility: New York Medical College ( Site 2023)
state: New York
city: Fargo
country: United States
facility: Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 2003)
state: North Dakota
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP) ( Site 2021)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Children's Hospital-Sanford Children's Specialty Clinic ( Site 2015)
state: South Dakota
city: Salt Lake City
country: United States
facility: Intermountain - Primary Children's Hospital ( Site 2014)
state: Utah
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital-Pediatrics ( Site 2972)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center-Pediatrics - Pedicatric Oncology ( Site 2973)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 2983)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: