Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)
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|ClinicalTrials.gov Identifier: NCT02628067|
Recruitment Status : Recruiting
First Posted : December 11, 2015
Last Update Posted : May 22, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Advanced Cancer Anal Carcinoma Anal Cancer Biliary Cancer Cholangiocarcinoma Bile Duct Cancer Neuroendocrine Tumor Carcinoid Tumor Endometrial Carcinoma Endometrial Cancer Cervical Carcinoma Cervical Cancer Vulvar Carcinoma Vulvar Cancer Small Cell Lung Carcinoma Small Cell Lung Cancer (SCLC) Mesothelioma Thyroid Carcinoma Thyroid Cancer Salivary Gland Carcinoma Salivary Gland Cancer Salivary Cancer Parotid Gland Cancer Advanced Solid Tumors Colorectal Carcinoma||Biological: pembrolizumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1609 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors (KEYNOTE 158)|
|Actual Study Start Date :||December 18, 2015|
|Estimated Primary Completion Date :||October 2, 2026|
|Estimated Study Completion Date :||October 2, 2026|
Experimental: Pembrolizumab 200 mg
Participants will receive pembrolizumab 200 mg intravenously on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years of treatment).
Experimental: Pembrolizumab 400 mg
Participants with any advanced solid tumor that has failed at least one line of therapy and is Tumor- Mutational Burden-High (TMB-H), excluding participants with mismatch repair deficient (dMMR/MSI-H) tumors. The dosing regimen for this cohort will be 400 mg every 6 weeks (Q6W) for up to 18 administrations (up to approximately 2 years of treatment).
- Objective Response Rate (ORR) [ Time Frame: Up to approximately 10.5 years ]ORR is defined as the percentage of participants who have 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 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ at any time during the trial. Responses will be determined by independent central radiologic review, with confirmatory assessment as required per RECIST 1.1. Participants with unknown or missing response information will be treated as non-responders. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.
- Duration of Response (DOR) [ Time Frame: Up to approximately 10.5 years ]DOR, defined in the subset of participants with a CR or PR, based on RECIST 1.1 as assessed by independent central radiologic review, as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death due to any cause, whichever occurs first. 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 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Participants who are alive, have not progressed, have not initiated new anti-cancer treatment, and have not been determined to be lost to follow-up are considered ongoing responders at the time of analysis.
- Progression Free Survival (PFS) [ Time Frame: Up to approximately 10.5 years ]PFS is defined as the time from allocation to the first documented disease progression according to RECIST 1.1 as assessed by independent central radiologic review, or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease (PD) is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. If a participant does not have a documented date of progression or death, PFS will be censored at the date of the last adequate assessment.
- Overall Survival (OS) [ Time Frame: Up to approximately 10.5 years ]OS is defined as the time from randomization to death due to any cause. OS will be presented. Censoring will be performed using the date of last known contact for those who are alive at the time of analysis.
- Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to approximately 27 months ]An adverse event (AE) is defined as any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this intervention. The percentage of participants with AEs will be reported.
- Percentage of Participants who Discontinue Study Intervention due to AEs [ Time Frame: Up to approximately 2 years ]An AE is defined as any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The percentage of participants who discontinue study intervention due to AEs will be reported.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Histologically or cytologically-documented, advanced solid tumor of one of the following types:
- Anal Squamous Cell Carcinoma
- Biliary Adenocarcinoma (gallbladder or biliary tree (intrahepatic or extrahepatic cholangiocarcinoma) except Ampulla of Vater cancers)
- Neuroendocrine Tumors (well- and moderately-differentiated) of the lung, appendix, small intestine, colon, rectum, or pancreas
- Endometrial Carcinoma (sarcomas and mesenchymal tumors are excluded)
- Cervical Squamous Cell Carcinoma
- Vulvar Squamous Cell Carcinoma
- Small Cell Lung Carcinoma
- Thyroid Carcinoma
- Salivary Gland Carcinoma (sarcomas and mesenchymal tumors are excluded)
- Any advanced solid tumor, with the exception of colorectal carcinoma (CRC), which is Microsatellite Instability (MSI)-High (MSI-H) OR
- Any advanced solid tumor (including Colorectal Carcinoma [CRC]) which is Mismatch Repair Deficient (dMMR)/MSI-H in participants from mainland China who are of Chinese descent. (CRC participants will have a histologically proven locally advanced unresectable or metastatic CRC which is dMMR/MSI-H that has received 2 prior lines of therapy) OR
- Any advanced solid tumor that has failed at least one line of therapy and is TMB-H (≥10 mut/Mb, F1CDx assay), excluding dMMR/MSI-H tumors.
Note: For participants to be eligible for enrollment they must have failed at least one line of standard of care systemic therapy (ie, not treatment naïve), with the exception of CRC participants who must have failed at least 2 lines of standard of care systemic therapy, as per CRC specific eligibility criteria. Participants must not have melanoma or NSCLC.
- Progression of tumor or intolerance to therapies known to provide clinical benefit. There is no limit to the number of prior treatment regimens
- Can supply tumor tissue for study analyses (dependent on tumor type)
- Radiologically-measurable disease
- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to first dose of pembrolizumab
- Life expectancy of at least 3 months
- Adequate organ function
- Female participants of childbearing potential must be willing to use adequate contraception during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: MK-3475 (120 days)
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment
- Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
- Active autoimmune disease that has required systemic treatment in the past 2 years
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from an adverse event caused by mAbs administered more than 4 weeks earlier
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of study Day 1 or not recovered from adverse events caused by a previously administered agent
- Known additional malignancy within 2 years prior to enrollment with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has known glioblastoma multiforme of the brain stem
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Active infection requiring systemic therapy
- Known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study
- Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
- Previously participated in any other pembrolizumab (MK-3475) study, or received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-Ligand 1 (anti-PD-L1), anti-PD-Ligand 2 (anti-PD-L2), or any other immunomodulating mAb or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- Known history of Human Immunodeficiency Virus (HIV)
- Known active Hepatitis B or C
- Received live vaccine within 30 days of planned start of study treatment
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
- Known history of active tuberculosis (TB, Bacillus tuberculosis)
- Has had an allogenic tissue/solid organ transplant.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02628067
|Contact: Toll Free Number||1-888-577-8839|
|Study Director:||Medical Director||Merck Sharp & Dohme LLC|
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Merck Sharp & Dohme LLC|
|Other Study ID Numbers:||
163196 ( Registry Identifier: JAPIC-CTI )
MK-3475-158 ( Other Identifier: Merck )
KEYNOTE-158 ( Other Identifier: Merck )
2022-500397-34-00 ( Registry Identifier: EU CT )
2015-002067-41 ( EudraCT Number )
|First Posted:||December 11, 2015 Key Record Dates|
|Last Update Posted:||May 22, 2023|
|Last Verified:||May 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
microsatellite instability (MSI)
mismatch repair (MMR)
Small Cell Lung Carcinoma
Salivary Gland Neoplasms
Bile Duct Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine System Diseases
Genital Neoplasms, Female
Neoplasms by Site
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications