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

NCT02821000 | Completed Phase 1 Results

• 3 other identifiers: 3475-151MK-3475-151KEYNOTE-151
• Study Type: interventional
• Target: 103
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Melanoma

Keywords

PD1; PD-1; PDL1; PD-L1

Outcome Measures

Primary Outcomes (3)

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

  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.

  Up to approximately 17 months (Through data cutoff date of 27-December-2017)

• Number of Participants Who Discontinued Study Treatment Due to an AE

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

  Up to approximately 17 months (through data cutoff date of 27-December-2017)

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

  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.

  Up to approximately 17 months (through data cutoff date of 27-December-2017)

Secondary Outcomes (17)

• Overall Survival (OS)

  Up to approximately 76 months

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

  Up to approximately 76 months

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

  Up to approximately 76 months

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

  Up to approximately 76 months

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

  Up to approximately 76 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

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).

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

Intravenous infusion

Also known as: MK-3475

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is of the Chinese descent, was born in China, and has a Chinese home address.
• Has histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma not amenable to local therapy.
• Participant may not have a diagnosis of uveal or ocular melanoma.
• Overall proportion of participants with mucosa melanoma will be no more than 22%.
• Has failed the first line chemotherapy (excluding adjuvant or neoadjuvant therapy) or targeted therapy for melanoma.
• Has at least one measurable lesion as defined by RECIST 1.1 on imaging studies (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]).
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Has an anticipated life expectancy of at least 3 months.
• Demonstrates adequate organ function.
• Has provided tissue for anti-programmed cell death ligand-1 (PD-L1) expression evaluation from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• Has documented BRAF mutation status or is willing to provide a tumor tissue for BRAF genotyping.
• Females may be enrolled in the study if they are:
• Of non-childbearing potential which is defined as:
• Is ≥45 years of age and has not had menses for greater than 2 years.
• Is amenorrheic for \<2 years without a hysterectomy and oophorectomy and has a follicle stimulating hormone (FSH) value in the postmenopausal range upon screening evaluation, and/or,

You may not qualify if:

• Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD-L1, anti-PD-L2 agents.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or baseline) from AEs due to agents administered more than 4 weeks earlier.
• Has had chemotherapy, targeted small molecule therapy, radiotherapy within 2 weeks prior to the first dose of study drug, or who has not recovered (i.e., ≤ Grade 1 or baseline) from AEs due to a previously administered agent.
• Has a known history of another (including unknown primary) malignancy within 5 years prior to first dose of study drug. (Exceptions include adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, superficial bladder cancer, or cancer in situ which has undergone potentially curative therapy.)
• Is expected to require any other form of systemic or localized antineoplastic therapy while in study.
• 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 (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study drug.
• Has an active infection requiring intravenous systemic therapy.
• Has received a live vaccine within 4 weeks prior to the first dose of study drug.
• Has a known hypersensitivity to the components of the study drug or another mAb.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Is known to be Human Immunodeficiency Virus (HIV) positive.
• Has known active Hepatitis B or C.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Si L, Zhang X, Shu Y, Pan H, Wu D, Liu J, Lou F, Mao L, Wang X, Wen X, Gu Y, Zhu L, Lan S, Cai X, Diede SJ, Zhou Y, Ge J, Li J, Wu H, Guo J. A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). Transl Oncol. 2019 Jun;12(6):828-835. doi: 10.1016/j.tranon.2019.02.007. Epub 2019 Apr 10.

  PMID: 30981094 RESULT

• Si L, Zhang X, Shu Y, Pan H, Wu D, Liu J, Mao L, Wang X, Wen X, Gu Y, Zhu L, Lan S, Cai X, Diede SJ, Dai H, Niu C, Li J, Guo J. Pembrolizumab in Chinese patients with advanced melanoma: 3-year follow-up of the KEYNOTE-151 study. Front Immunol. 2022 Oct 11;13:882471. doi: 10.3389/fimmu.2022.882471. eCollection 2022.

  PMID: 36304457 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2016
• First Posted: July 1, 2016
• Study Start: July 8, 2016
• Primary Completion: December 27, 2017
• Study Completion: November 30, 2022
• Last Updated: May 30, 2024
• Results First Posted: March 21, 2019

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share