Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants receive pembrolizumab 2 mg/kg intravenously on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).

Medical Director

The purpose of this study is to determine the safety, tolerability, and objective response rate (ORR) of pembrolizumab (MK-3475) in Chinese participants with locally advanced or metastatic melanoma, with disease progression following first line chemotherapy or targeted therapy. ORR will be based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

With Amendment 6 (effective date 18-Mar-2022), once the study objectives have been met or the study has ended, participants will be discontinued from this study and may be enrolled in an extension study to continue protocol-defined assessments and treatment.

Safety and Efficacy Study of Pembrolizumab (MK-3475) in Chinese Participants With Locally Advanced or Metastatic Melanoma (MK-3475-151/KEYNOTE-151)

A Phase Ib Study of Pembrolizumab (MK-3475) in Chinese Subjects With Locally Advanced or Metastatic Melanoma (Keynote-151)

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented.

The number of all participants who discontinued study treatment due to an AE is presented.

ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 assessed by blinded independent central review (BICR). The ORR per RECIST 1.1 for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants.

OS was defined as the time from first day of study treatment to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months.

PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per RECIST 1.1 for participants is presented.

DOR was defined as the time from first documented evidence of Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until disease progression or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months.

ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or a Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST assessed by blinded independent central review (BICR). The ORR per irRECIST for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants.

PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRECIST based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per irRECIST for participants is presented.

DOR was defined as the time from first documented evidence of Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST until disease progression or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. DOR assessments were based on blinded independent central review (BICR). DOR was analyzed using the Kaplan-Meier method and is reported in months.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 2 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 2 is presented.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 4 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 4 is presented.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 6 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 6 is presented.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 8 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 8 is presented.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 12 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 12 is presented.

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 16 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 16 is presented.

Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 1 (21-day cycle). The Cmax of pembrolizumab is presented.

Blood samples were obtained for PK analysis of the Cmax of pembrolizumab 30 minutes after the end of infusion during Cycle 8 (21-day cycle). The Cmax of pembrolizumab is presented.

Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 1 day after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented.

Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 5 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented.

Blood samples were obtained for PK analysis of the serum concentration of pembrolizumab 14 days after the end of infusion during Cycle 1 (21-day cycle). The serum concentration of pembrolizumab is presented.

Merck Sharp & Dohme LLC

The safety population consisted of all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered a serious AE (SAE) unless considered related to study treatment. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as SAEs. One person who withdrew from the study (see participant flow) subsequently died.

Participants received pembrolizumab 2 mg/kg IV on Day 1 of each 21-day cycle.

Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 2 mg/kg on day 1 of each 21-day cycle.

Pembrolizumab Second Course

Participants received pembrolizumab 2 mg/kg intravenous (IV) on Day 1 of each 21-day cycle. Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 2 mg/kg on day 1 of each 21-day cycle.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Participants were assessed for their PD-L1 tumor expression status by immunohistochemistry assay using archival tumor tissue or tumor tissue from a newly obtained biopsy. The PD-L1 tumor expression status of participants is presented.

Programmed Cell Death-Ligand 1 (PD-L1) Expression Status

Participants were assessed for ECOG PS: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory \& able to carry out work of a light or sedentary nature; Grade 2: Ambulatory \& capable of all selfcare but unable to carry out any work activities, up \& about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled, cannot carry on any selfcare, totally confined to bed or chair or Grade 5: Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

BRAF mutation status was required from all participants. For participants that did not have a prior documented BRAF mutation status, BRAF V600 mutation analysis was performed by polymerase chain reaction (PCR) on tumor tissue. The BRAF mutation status of participants is presented.

BRAF Mutation Expression Status

Senior Vice President, Global Clinical Development

The safety population consisted of all participants who received at least one dose of study treatment.

Number of Participants Who Experienced At Least One Adverse Event (AE)

Number of Participants Who Discontinued Study Treatment Due to an AE

The analysis population consisted of all participants who received at least one dose of study treatment and had measurable disease at baseline.

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

The analysis population consisted of all participants who received at least one dose of study treatment.

Overall Survival (OS)

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

The analysis population consisted of all participants who received at least one dose of study treatment, had measurable disease at baseline, and had confirmed CR or PR.

Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

Objective Response Rate (ORR) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

Progression-free Survival (PFS) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

Duration of Response (DOR) by Immune-related Response Evaluation Criteria in Solid Tumors Version (irRECIST)

The analysis population consisted of participants who received 1 dose of study treatment, completed Cycle 1 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 2 (21-day Cycle)

The analysis population consisted of participants who received 3 doses of study treatment, completed Cycle 3 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 4 (21-day Cycle)

The analysis population consisted of participants who received 5 doses of study treatment, completed Cycle 5 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 6 (21-day Cycle)

The analysis population consisted of participants who received 7 doses of study treatment, completed Cycle 7 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 8 (21-day Cycle)

The analysis population consisted of participants who received 11 doses of study treatment, completed Cycle 11 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 12 (21-day Cycle)

The analysis population consisted of participants who received 15 doses of study treatment, completed Cycle 15 (21-day cycle), and had blood samples drawn for Ctrough analysis.

Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 16 (21-day Cycle)

The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for Cmax analysis.

Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 1 (21-day Cycle)

The analysis population consisted of participants who received 8 doses of study treatment and had blood samples drawn for Cmax analysis.

Observed Maximum Serum Concentration (Cmax) of Pembrolizumab 30 Minutes After The End of Infusion During Cycle 8 (21-day Cycle)

The analysis population consisted of participants who received 1 dose of study treatment in Cycle 1 (21-day cycle) and had blood samples drawn for serum concentration of pembrolizumab.

Spots Global Cancer Trial Database for Safety and Efficacy Study of Pembrolizumab (MK-3475) in Chinese Participants With Locally Advanced or Metastatic Melanoma (MK-3475-151/KEYNOTE-151)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial