A Study of Pembrolizumab in Japanese Pediatric Participants With Solid Tumors or Lymphomas and Japanese Adult Participants With Merkel Cell Carcinoma (MK-3475-G21/KEYNOTE-G21)

Official title

A Phase I/II Study of Pembrolizumab (MK-3475) in Japanese Pediatric Participants With Specific Solid Tumors or Lymphomas, or in Japanese Adult Participants With Advanced Merkel Cell Carcinoma (KEYNOTE-G21)

Overview

Researchers are looking for new ways to treat people with solid tumors, lymphomas (blood cancers), and a certain type of skin cancer. The goals of this study are to learn: * About the safety of pembrolizumab (the study medicine) and if people tolerate it * What happens to different doses of pembrolizumab in a person's body over time * How the cancer responds (gets smaller or goes away) to treatment

Interventions

• Biological Pembrolizumab
  25 mg/mL solution for intravenous infusion.

Primary outcome measures

• Arm 1: Number of Participants Who Experience an Adverse Event (AE) [Time frame: Up to approximately 28 months]
• Arm 1: Number of Participants Who Discontinue Study Treatment Due To an AE [Time frame: Up to approximately 25 months]
• Arm 1: Area Under the Concentration-Time Curve (AUC) of Pembrolizumab [Time frame: Predose at Cycle 1, 2, 4, 8 and every 4 cycles thereafter up to 35 cycles; postdose at Cycle 1 and Cycle 8 (a cycle is 21 days)]
• Arm 1: Maximum Concentration (Cmax) of Pembrolizumab [Time frame: Predose at Cycle 1, 2, 4, 8 and every 4 cycles thereafter up to 35 cycles; postdose at Cycle 1 and Cycle 8 (a cycle is 21 days)]
• Arm 1: Minimum Plasma Concentration (Cmin) of Pembrolizumab [Time frame: Predose at Cycle 1, 2, 4, 8 and every 4 cycles thereafter up to 35 cycles; postdose at Cycle 1 and Cycle 8 (a cycle is 21 days)]
• Arm 2: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) [Time frame: Up to approximately 37 months]

Secondary outcome measures (12)

• Arm 1: ORR per RECIST 1.1 by Investigator Assessment [Time frame: Up to approximately 46 months]
• Arm 1: ORR per Lugano Classification by Investigator Assessment [Time frame: Up to approximately 46 months]
• Arm 1: Duration of Response (DOR) per RECIST 1.1 by Investigator Assessment [Time frame: Up to approximately 46 months]
• Arm 1: DOR per Lugano Classification by Investigator Assessment [Time frame: Up to approximately 46 months]
• Arm 1: Disease Control (DCR) per RECIST 1.1 by Investigator Assessment [Time frame: Up to approximately 46 months]
• Arm 1: DCR per Lugano Classification by Investigator Assessment [Time frame: Up to approximately 46 months]
• Arm 1: Progression-free Survival (PFS) per RECIST 1.1 by Investigator Assessment [Time frame: Up to approximately 46 months]
• Arm 1: PFS per Lugano Classification by Investigator Assesment [Time frame: Up to approximately 46 months]
• Arm 1: Relapse-free Survival (RFS) per RECIST 1.1 by Investigator Assessment [Time frame: Up to approximately 46 months]
• Arm 1: Distant Metastasis-free Survival (DMFS) per RECIST 1.1 by Investigator Assessment [Time frame: Up to approximately 46 months]
• Arm 1: Overall Survival (OS) [Time frame: Up to approximately 46 months]
• Arm 1: Number of Participants with Anti-Drug Antibodies (ADAs) Against Pembrolizumab [Time frame: Predose at Cycle 1, 2, 4, 8 and every 4 cycles thereafter up to 35 cycles (a cycle is 21 days)]

Eligibility criteria

Inclusion criteria

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

Arm 1:

• For participants with relapsed or refractory classical Hodgkin lymphoma (cHL) or primary mediastinal large B-cell lymphoma (PMBCL)

• Has a confirmed diagnosis of relapsed or refractory cHL or PMBCL after the most recent therapy
• Has radiographically measurable disease per Lugano classification
• For participants with completely resected melanoma:

• Has surgically completely resected and histologically/pathologically confirmed diagnosis of Stage IIB, IIC, III or IV cutaneous melanoma
• Has not received any prior systemic therapy for their melanoma beyond surgical resection
• All suspicious lesions amenable to biopsy are confirmed negative for malignancy
• For participants with locally advanced or metastatic melanoma:

• Has histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma (including acral) not amenable to local therapy
• Has radiographically measurable lesion(s) as defined by RECIST 1.1
• For participants with microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) solid tumors:

• Has histologically/cytologically documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the participant and treating physician
• Has a documented positive local MSI-H or dMMR test result
• Has radiographically measurable disease based on RECIST 1.1
• For participants with tumor mutational burden-high (TMB-H) solid tumors:

• Has histologically/cytologically documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the participant and treating physician
• Has radiographically measurable disease based on RECIST 1.1
• For participants with MCC:

• Has histologically confirmed diagnosis of locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy and is not amenable to local therapy or metastatic MCC (Stage IV)
• Has radiographically measurable disease based on RECIST 1.1

Arm 2:

• For participants with MCC:

• Has been untreated for advanced or metastatic disease

Arm 1 \& Arm 2:

• Life expectancy of >3 months (Arm 1) or >6 months (Arm 2)

Exclusion criteria

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

• Has known additional malignancy that is progressing or has required active treatment
• Has known active (central nervous system) CNS metastases and/or carcinomatous meningitis
• Has active autoimmune disease that has required systemic treatment in past 2 years
• Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has active infection requiring systemic therapy
• Has known history of human immunodeficiency virus (HIV) infection
• Has known history of Hepatitis B infection or known active Hepatitis C virus
• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years
• Has not adequately recovered from major surgery or has ongoing surgical complications

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Japan · 7 centers

• Nagoya City University Hospital ( Site 0003) — Nagoya
• Nagoya City University Hospital ( Site 0007) — Nagoya
• Sapporo Hokuyu Hospital ( Site 0005) — Sapporo
• Hyogo Prefectural Kobe Children's Hospital ( Site 0006) — Kobe
• National Cancer Center Hospital ( Site 0002) — Chūō
• National Hospital Organization Kyushu Cancer Center ( Site 0001) — Fukuoka
• University Hospital,Kyoto Prefectural University of Medicine ( Site 0004) — Kyoto

Identifiers

NCT: NCT07302347 · 3475-G21 · MK-3475-G21 · jRCT2041250120

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗