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 : April 29, 2024

See Contacts and Locations

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme LLC

Tracking Information

First Submitted Date ^ICMJE

December 9, 2015

First Posted Date ^ICMJE

December 11, 2015

Last Update Posted Date

April 29, 2024

Actual Study Start Date ^ICMJE

December 18, 2015

Estimated Primary Completion Date

May 4, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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.

Original Primary Outcome Measures ^ICMJE

Objective Response Rate (ORR) [ Time Frame: Up to 5 years ]

Change History

Current Secondary Outcome Measures ^ICMJE

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.

Original Secondary Outcome Measures ^ICMJE

Not Provided

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)

Official Title ^ICMJE

A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors (KEYNOTE 158)

Brief Summary

In this study, participants with multiple types of advanced (unresectable and/or metastatic) solid tumors who have progressed on standard of care therapy will be treated with pembrolizumab (MK-3475).

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

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

Intervention ^ICMJE

Biological: pembrolizumab

intravenous infusion

Other Names:

MK-3475
SCH 900475
KEYTRUDA®

Study Arms ^ICMJE

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).

Intervention: Biological: pembrolizumab
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).

Intervention: Biological: pembrolizumab

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

1609

Original Estimated Enrollment ^ICMJE

1100

Estimated Study Completion Date ^ICMJE

May 4, 2027

Estimated Primary Completion Date

May 4, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

- 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
Mesothelioma
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)

Exclusion Criteria:

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.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Toll Free Number

1-888-577-8839

Listed Location Countries ^ICMJE

Australia, Brazil, Canada, Chile, Colombia, Denmark, France, Germany, Israel, Italy, Korea, Republic of, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Portugal, Russian Federation, South Africa, Spain, Taiwan, United States

Removed Location Countries

China, Japan, United Kingdom

Administrative Information

NCT Number ^ICMJE

NCT02628067

Other Study ID Numbers ^ICMJE

3475-158
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 )

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL:	http://engagezone.msd.com/ds_documentation.php

Current Responsible Party

Merck Sharp & Dohme LLC

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Merck Sharp & Dohme LLC

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Medical Director

Merck Sharp & Dohme LLC

PRS Account

Merck Sharp & Dohme LLC

Verification Date

April 2024

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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