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History of Changes for Study: NCT02628067
Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)
Latest version (submitted May 9, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 December 9, 2015 None (earliest Version on record)
2 December 17, 2015 Conditions and Study Status
3 January 4, 2016 Recruitment Status, Study Status and Contacts/Locations
4 January 21, 2016 Study Status and Contacts/Locations
5 February 2, 2016 Study Status and Contacts/Locations
6 February 11, 2016 Contacts/Locations and Study Status
7 February 17, 2016 Contacts/Locations and Study Status
8 February 24, 2016 Contacts/Locations and Study Status
9 March 3, 2016 Study Status and Contacts/Locations
10 March 16, 2016 Contacts/Locations, Study Status and Study Identification
11 March 23, 2016 Study Status and Contacts/Locations
12 April 7, 2016 Contacts/Locations, Arms and Interventions, Study Status, Eligibility and Outcome Measures
13 April 12, 2016 Study Status
14 May 5, 2016 Contacts/Locations and Study Status
15 May 24, 2016 Eligibility and Study Status
16 June 2, 2016 Study Status and Contacts/Locations
17 June 16, 2016 Contacts/Locations and Study Status
18 June 22, 2016 Contacts/Locations and Study Status
19 June 28, 2016 Contacts/Locations and Study Status
20 July 15, 2016 Study Status and Contacts/Locations
21 July 22, 2016 Contacts/Locations and Study Status
22 August 3, 2016 Study Status and Contacts/Locations
23 August 25, 2016 Contacts/Locations and Study Status
24 October 4, 2016 Study Status and Contacts/Locations
25 October 13, 2016 Contacts/Locations and Study Status
26 November 10, 2016 Contacts/Locations and Study Status
27 November 18, 2016 Contacts/Locations and Study Status
28 January 2, 2017 Study Status
29 February 3, 2017 Contacts/Locations and Study Status
30 February 23, 2017 Study Status and Contacts/Locations
31 June 13, 2017 Study Status, Oversight, Contacts/Locations, Eligibility, Outcome Measures and Study Design
32 August 30, 2017 Study Status
33 September 21, 2017 Contacts/Locations and Study Status
34 October 10, 2017 Contacts/Locations, Study Status and Eligibility
35 November 17, 2017 Study Status
36 December 21, 2017 Study Status and Contacts/Locations
37 January 18, 2018 Study Status and Contacts/Locations
38 January 31, 2018 Contacts/Locations and Study Status
39 February 6, 2018 Study Status and Contacts/Locations
40 May 11, 2018 Contacts/Locations and Study Status
41 May 29, 2018 Contacts/Locations and Study Status
42 June 7, 2018 Contacts/Locations and Study Status
43 June 27, 2018 Contacts/Locations and Study Status
44 September 21, 2018 Study Status and Contacts/Locations
45 January 18, 2019 Study Status, IPDSharing and Contacts/Locations
46 March 8, 2019 Contacts/Locations and Study Status
47 May 22, 2019 Study Status and Contacts/Locations
48 July 18, 2019 Study Status and Contacts/Locations
49 December 19, 2019 Study Status, Arms and Interventions, References, Contacts/Locations, Eligibility, Outcome Measures, Study Design, Conditions, Study Description and Study Identification
50 December 27, 2019 Contacts/Locations and Study Status
51 January 27, 2020 Study Status and Contacts/Locations
52 February 14, 2020 Study Status, References and Contacts/Locations
53 May 14, 2020 Study Status and Contacts/Locations
54 July 26, 2020 Arms and Interventions, Study Design, Outcome Measures, Conditions, Study Status and Eligibility
55 September 23, 2020 Study Status and Contacts/Locations
56 November 5, 2020 Study Status and Contacts/Locations
57 December 16, 2020 Contacts/Locations and Study Status
58 February 19, 2021 Contacts/Locations and Study Status
59 March 2, 2021 Contacts/Locations and Study Status
60 April 30, 2021 Study Status and Contacts/Locations
61 June 23, 2021 Study Status and Eligibility
62 August 25, 2021 Study Status and Contacts/Locations
63 October 20, 2021 Study Status and Contacts/Locations
64 December 17, 2021 Study Status and Contacts/Locations
65 January 21, 2022 Study Status and Contacts/Locations
66 April 8, 2022 Contacts/Locations and Study Status
67 April 13, 2022 Contacts/Locations and Study Status
68 May 13, 2022 Study Status and Contacts/Locations
69 May 20, 2022 Contacts/Locations and Study Status
70 May 24, 2022 Contacts/Locations and Study Status
71 June 7, 2022 Study Status, Eligibility, Study Design and Study Identification
72 July 13, 2022 Contacts/Locations and Study Status
73 October 21, 2022 Outcome Measures, Study Status and Arms and Interventions
74 November 23, 2022 Study Status and Contacts/Locations
75 January 18, 2023 Outcome Measures, Study Status and Contacts/Locations
76 March 16, 2023 Study Status
77 May 5, 2023 Study Status and Contacts/Locations
78 May 19, 2023 Eligibility and Study Status
79 June 23, 2023 Study Status and Contacts/Locations
80 June 28, 2023 References and Study Status
81 November 2, 2023 Study Status and Contacts/Locations
82 November 23, 2023 Contacts/Locations and Study Status
83 December 28, 2023 Study Status and Contacts/Locations
84 February 2, 2024 Study Status and Contacts/Locations
85 April 4, 2024 Study Status and Contacts/Locations
86 April 26, 2024 Study Status
87 May 9, 2024 Study Status and Contacts/Locations
Comparison Format:

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Study NCT02628067
Submitted Date:  July 13, 2022 (v72)

Open or close this module Study Identification
Unique Protocol ID: 3475-158
Brief Title: Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)
Official Title: A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors (KEYNOTE 158)
Secondary IDs: 163196 [Registry Identifier: JAPIC-CTI]
MK-3475-158 [Merck]
KEYNOTE-158 [Merck]
2022-500397-34-00 [Registry Identifier: EU CT]
2015-002067-41 [EudraCT Number]
Open or close this module Study Status
Record Verification: July 2022
Overall Status: Recruiting
Study Start: December 18, 2015
Primary Completion: June 18, 2026 [Anticipated]
Study Completion: June 18, 2026 [Anticipated]
First Submitted: December 9, 2015
First Submitted that
Met QC Criteria:
December 9, 2015
First Posted: December 11, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
July 13, 2022
Last Update Posted: July 14, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Merck Sharp & Dohme LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
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:
Open or close this module Conditions
Conditions: 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
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
microsatellite instability (MSI)
mismatch repair (MMR)
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 1609 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Pembrolizumab 200 mg
Participants 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).
Biological: pembrolizumab
intravenous infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
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).
Biological: pembrolizumab
intravenous infusion
Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Objective Response Rate (ORR)
[ Time Frame: Up to approximately 2 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.
Secondary Outcome Measures:
1. Duration of Response (DOR)
[ Time Frame: Up to approximately 2 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.
2. Progression Free Survival (PFS)
[ Time Frame: Up to approximately 2 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, 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.
3. Overall Survival (OS)
[ Time Frame: Up to approximately 2 years ]

OS was defined as the time from randomization to death due to any cause. OS is presented. Censoring will be performed using the date of last known contact for those who are alive at the time of analysis.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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.
Open or close this module Contacts/Locations
Central Contact Person: Toll Free Number
Telephone: 1-888-577-8839
Study Officials: Medical Director
Study Director
Merck Sharp & Dohme LLC
Locations: United States, California
Call for Information (Investigational Site 0202)
[Recruiting]
Los Angeles, California, United States, 90033
Call for Information (Investigational Site 0017)
[Recruiting]
Los Angeles, California, United States, 90048
United States, Florida
Call for Information (Investigational Site 0015)
[Recruiting]
Orlando, Florida, United States, 32806
United States, Massachusetts
Call for Information (Investigational Site 0010)
[Recruiting]
Boston, Massachusetts, United States, 02215
United States, New Jersey
Call for Information (Investigational Site 0008)
[Recruiting]
New Brunswick, New Jersey, United States, 08903
Australia
Merck Sharp & Dohme
[Recruiting]
North Ryde, Australia
Contact:Contact: Australian Medical Information Centre 61 2 8988 8428
Brazil
MSD Brasil
[Recruiting]
Sao Paulo, Brazil
Contact:Contact: MSD Online 0800 012 22 32
Canada, Quebec
Merck Canada
[Recruiting]
Kirkland, Quebec, Canada, H9H 4M7
Contact:Contact: Medical Information Centre Centre d'information medicale Merck Canada Inc. 514-428-8600 / 1-800-567-2594
China
Merck Sharp & Dohme (China) Ltd.
[Recruiting]
Beijing, China
Contact:Contact: Zaiqi Wang +86 10 5860 9288
Colombia
MDS Colombia SAS
[Recruiting]
Bogota, Colombia
Contact:Contact: Francesca Carvajal 57 1219109011090
Denmark
Merck Sharp & Dohme
[Recruiting]
Glostrup, Denmark
Contact:Contact: Artur Fijolek 45 21387145
France
MSD France
[Recruiting]
Paris, France
Contact:Contact: Dominique Blazy 33 147548990
Germany
MSD Sharp & Dohme GmbH
[Recruiting]
Haar, Germany
Contact:Contact: German Medical Information Center 49 800 673 673 673
Israel
Merck Sharp & Dohme Co. Ltd.
[Recruiting]
Hod Hasharon, Israel
Contact:Contact: Gally Teper 972-9-9533310
Italy
MSD Italia S.r.l.
[Recruiting]
Rome, Italy
Contact:Contact: Barbara Capaccetti 39 06361911
Korea, Republic of
MSD Korea LTD
[Recruiting]
Seoul, Korea, Republic of, 4130
Contact:Contact: Jongho Ahn 82-2-331-2000 2015
Mexico
MSD
[Recruiting]
Mexico City, Mexico
Contact:Contact: Juan Marques 52 55254819608
Netherlands
Merck Sharp & Dohme BV
[Recruiting]
Haarlem, Netherlands
Contact:Contact: Caroline Doornebos 31 23 515 3362
Norway
MSD Norge A/S
[Recruiting]
Drammen, Norway
Contact:Contact: Tony Johansson 47 32 20 75 20
Philippines
Merck Sharp & Dohme (I.A.) Corporation
[Recruiting]
Makati, Philippines
Contact:Contact: Cesar Recto 632 784 9500
Russian Federation
Merck Sharp & Dohme IDEA, Inc.
[Recruiting]
Moscow, Russian Federation
Contact:Contact: Tatiana Serebriakova 74959167100, EXT.366
South Africa
MSD (Pty) LTD South Africa
[Recruiting]
Midrand, South Africa
Contact:Contact: Khanyi Mzolo 27 11 655 3140
Spain
Merck Sharp and Dohme de Espana S.A.
[Recruiting]
Madrid, Spain
Contact:Contact: Lourdes Lopez-Bravo (0034) 913210654
Taiwan
Merck Sharp & Dohme (I.A.) Corp.
[Recruiting]
Taipei, Taiwan
Contact:Contact: I-Hua Su 886-2-66316000
Open or close this module IPDSharing
Plan to Share IPD: Yes
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Supporting Information:
Time Frame:
Access Criteria:
URL: http://engagezone.msd.com/ds_documentation.php
Open or close this module References
Citations: [Study Results] Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020 Jan 1;38(1):1-10. doi: 10.1200/JCO.19.02105. Epub 2019 Nov 4. PubMed 31682550
Links: Description: Merck Oncology Clinical Trials Information
Available IPD/Information:

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