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Clinical Trials List

Protocol NumberMK-3475-158
NCT Number(ClinicalTrials.gov Identfier)NCT02628067

2015-12-01 - 2026-12-31

Phase II

Recruiting8

ICD-10C80.1

Malignant (primary) neoplasm, unspecified

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

  • Trial Applicant

    Merck Sharp & Dohme (I.A.) LLC

  • Sponsor

    Merck Sharp & Dohme Corp.

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator 鍾奇峰 Division of Hematology & Oncology
Koo Foundation Sun Yat-Sen Cancer Center

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chia-Chi Lin Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Audit

None

Principal Investigator Chia-Jui Yen Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Jen-Shi Chen Division of Hematology & Oncology
Linkou Chang Gung Medical Foundation

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Ming-Huang Chen Division of Hematology & Oncology
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chien-Hsing Lu Division of Obstetrics & Gynecology
Taichung Veterans General Hospital

Co-Principal Investigator

  • 黃曉峰 Division of Obstetrics & Gynecology
  • 劉芝谷 Division of Obstetrics & Gynecology
  • 孫珞 Division of Obstetrics & Gynecology
  • 許世典 Division of Obstetrics & Gynecology
  • 吳振豪 Division of Obstetrics & Gynecology
  • 石宇翔 Division of Obstetrics & Gynecology

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Jih-Hsiang Lee Division of Hematology & Oncology
National Taiwan University Hospital Hsin-Chu Branch

Co-Principal Investigator

  • 吳旭 Division of Hematology & Oncology
  • 楊明翰 Division of Hematology & Oncology
  • 楊博鈞 Division of Hematology & Oncology

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 馮盈勳 Division of Hematology & Oncology
Chi Mei Medical Center

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Condition/Disease

Advanced Solid Tumors

Objectives

1. Primary Objective(s) & Hypothesis(es) Objective 1: To evaluate the ORR to pembrolizumab, based on RECIST 1.1 as assessed by independent central radiologic review, in biomarker-unselected subjects with any one of multiple types of advanced (metastatic and/or unresectable) solid tumors (Groups A-J) Objective 2: To evaluate the ORR to pembrolizumab, based on RECIST 1.1 as assessed by independent central radiologic review, in biomarker-selected subjects with any one of multiple types of advanced (metastatic and/or unresectable) solid tumors (Groups A-K). The primary biomarkers to be evaluated are (1) tumor expression of PD-L1 by IHC (Groups A-J), (2) tumor GEP by RNA analysis (Groups A-J), and (3) tumor MSI-H (Groups A-K). 2. Secondary Objective(s) & Hypothesis(es)

Test Drug

Pembrolizumab (MK-3475)

Active Ingredient

Pembrolizumab

Dosage Form

Injection

Dosage

100mg

Endpoints

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.

Inclution Criteria

Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
(1) Be willing and able to provide written informed consent/assent for the trial.
The subject may also provide consent/assent for Future Biomedical Research.
However, the subject may participate in the main trial without participating in
Future Biomedical Research.
(2) Be ≥18 years of age on the day of signing informed consent.
(3) Have a histologically or cytologically-documented, advanced (metastatic
and/or unresectable) solid tumor that is incurable and for which prior standard
first-line treatment has failed. Patients must have progressed on or be intolerant
to therapies that are known to provide clinical benefit. There is no limit to the
number of prior treatment regimens.
Note: Prior neoadjuvant or adjuvant therapy included in initial treatment
may not be considered first- or later-line SOC treatment unless such
treatments were completed less than 12 months prior to the current tumor
recurrence.
(4) Have one of the following advanced (unresectable and/or metastatic) tumor
types:
((A) Anal Squamous Cell Carcinoma,
(B) Biliary Adenocarcinoma (gallbladder or biliary tree (intrahepatic
or extrahepatic cholangiocarcinoma) except Ampulla of Vater
Cancers,
(C) Neuroendocrine Tumors (well- and moderately-differentiated), of
the lung, appendix, small intestine, colon, rectum, or pancreas,
(D) Endometrial Carcinoma (sarcomas and mesenchymal tumors are
excluded),
(E) Cervical Squamous Cell Carcinoma,
(F) Vulvar Squamous Cell Carcinoma,
(G) Small Cell Lung Carcinoma,
(H) Mesothelioma (Malignant Pleural Mesothelioma),
(I) Thyroid Carcinoma (Papillary or Follicular Subtypes),
(J) Salivary Gland Carcinoma (sarcomas and mesenchymal tumors are
excluded)
OR
(K) Any other advanced solid tumor (except CRC), which is MSI-H.
(5) Have submitted an evaluable tissue sample for biomarker analysis from a
tumor lesion not previously irradiated (exceptions may be considered after
Sponsor consultation). (See Procedure Manual for detailed instructions).
The tumor tissue submitted for analysis must be from a single tumor tissue
specimen and of sufficient quantity and quality to allow assessment of ALL
required primary biomarkers.
Note: SUBJECTS WILL NOT BE ELIGIBLE TO ENROLL INTO
GROUPS A-J UNLESS ALL THREE PRIMARY BIOMARKERS
(TUMOR PD-L1 EXPRESSION, GEP SCORE, and MSI-H STATUS)
CAN BE ASSESSED USING TISSUE FROM THE SAME SINGLE
TUMOR SPECIMEN.
(6) If enrollment in Groups A-J has moved to biomarker enrichment, have a tumor
that is positive for one or more of the pre-specified primary biomarker(s), as
assessed by the central laboratory. These enrichment biomarkers may be
PD-L1 expression by IHC (at a percentage to be prespecified), a positive tumor
RNA GEP score (at a prespecified cut-off), and/or tumor MSI-H.
(7) Have radiologically measurable disease based on RECIST 1.1. Independent
central radiologic review must confirm the presence of radiologically
measureable disease based on RECIST 1.1 for the subject to be eligible to
participate in the trial (see Site Imaging Manual for detailed instructions).
Tumor lesions situated in a previously irradiated area are considered
measurable if progression has been demonstrated in such lesions.
(8) Have a performance status of 0 or 1 on the ECOG Performance Scale.
(9) Demonstrate adequate organ function as defined in Table 1.
(10) Female subjects of childbearing potential must have a negative urine or
serum pregnancy test within 72 hours prior to receiving the first dose of trial
medication. If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
(11) Female subjects of childbearing potential (See Section 5.7.2) must be willing
to use an adequate method of contraception, as outlined in Section 5.7.2. –
Contraception, for the course of the study through 120 days after the last dose
of trial medication.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception method for the subject.
(12) Male subjects of childbearing potential (See Section 5.7.2.) must agree to use
an adequate method of contraception, as outlined in Section 5.7.2. –
Contraception, for the course of the study through 120 days after the last dose
of trial medication.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception method for the subject.

Exclusion Criteria

Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
(1) 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 treatment.
(2) Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior to the
first dose of trial treatment. The use of physiologic doses of corticosteroids
may be approved after consultation with the Sponsor.
(3) Has an active autoimmune disease that has required systemic treatment in the
past 2 years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment.
(4) Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior
to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from
an AE due to mAbs administered more than 4 weeks earlier.
(5) Has had prior chemotherapy, targeted small molecule therapy, or radiation
therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤
Grade 1 or at baseline) from an AE due to a previously administered agent.
i. Note: Subjects with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia
are an exception to this criterion and may qualify for the trial.
ii. Note: If a subject has undergone major surgery, that subject must
have recovered adequately from any toxicity and/or complications
from this procedure prior to starting therapy.
(6) Has a 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 cervical and/or in situ
breast cancers.
(7) Has known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain metastases
may participate provided these brain metastases are stable (without evidence
of progression by imaging over a period of at least 4 weeks and any neurologic
symptoms have returned to baseline), they have no evidence of new or
enlarging brain metastases (confirmed by imaging within 28 days of the first
dose of trial treatment), and they are not using steroids for at least 7 days prior
to trial treatment. This exception does not include carcinomatous meningitis
which is excluded regardless of clinical stability.
(8) Has evidence of active non-infectious pneumonitis.
(9) Has an active infection requiring systemic therapy.
(10) Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject’s participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.
(11) Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
(12) Is pregnant or breastfeeding, or expecting to conceive or father children within
the projected duration of the trial, starting with the screening visit through 120
days after the last dose of trial treatment.
(13) Has previously participated in any other pembrolizumab (MK-3475) trial, or
received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or any
other immune-modulating mAb (including ipilimumab and any other antibody
or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
(14) Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
antibodies).
(15) Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g.,
HCV RNA [qualitative] is detected).
(16) Has received a live vaccine within 30 days of planned start of study therapy.
Note: The killed virus vaccines used for seasonal influenza vaccines for
injection are allowed; however intranasal influenza vaccines (e.g., FluMist® )
are live attenuated vaccines and are not allowed.

The Estimated Number of Participants

  • Taiwan

    30 participants

  • Global

    1595 participants

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