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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02628067




Registration number
NCT02628067
Ethics application status
Date submitted
9/12/2015
Date registered
11/12/2015

Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)
Scientific title
A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors (KEYNOTE 158)
Secondary ID [1] 0 0
163196
Secondary ID [2] 0 0
3475-158
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Anal Carcinoma 0 0
Anal Cancer 0 0
Biliary Cancer 0 0
Cholangiocarcinoma 0 0
Bile Duct Cancer 0 0
Neuroendocrine Tumor 0 0
Carcinoid Tumor 0 0
Endometrial Carcinoma 0 0
Endometrial Cancer 0 0
Cervical Carcinoma 0 0
Cervical Cancer 0 0
Vulvar Carcinoma 0 0
Vulvar Cancer 0 0
Small Cell Lung Carcinoma 0 0
Small Cell Lung Cancer (SCLC) 0 0
Mesothelioma 0 0
Thyroid Carcinoma 0 0
Thyroid Cancer 0 0
Salivary Gland Carcinoma 0 0
Salivary Gland Cancer 0 0
Salivary Cancer 0 0
Parotid Gland Cancer 0 0
Advanced Solid Tumors 0 0
Colorectal Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Thyroid
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Bowel - Anal
Cancer 0 0 0 0
Other cancer types
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - pembrolizumab
Treatment: Other - pembrolizumab

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).


Treatment: Other: pembrolizumab
intravenous infusion

Treatment: Other: pembrolizumab
intravenous infusion

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 10.5 years
Secondary outcome [1] 0 0
Duration of Response (DOR)
Timepoint [1] 0 0
Up to approximately 10.5 years
Secondary outcome [2] 0 0
Progression Free Survival (PFS)
Timepoint [2] 0 0
Up to approximately 10.5 years
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Up to approximately 10.5 years
Secondary outcome [4] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [4] 0 0
Up to approximately 27 months
Secondary outcome [5] 0 0
Percentage of Participants who Discontinue Study Intervention due to AEs
Timepoint [5] 0 0
Up to approximately 2 years

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
MSD Australia - North Ryde
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Brazil
State/province [2] 0 0
Sao Paulo
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
Chile
State/province [4] 0 0
Santiago
Country [5] 0 0
Colombia
State/province [5] 0 0
Bogota
Country [6] 0 0
Denmark
State/province [6] 0 0
Glostrup
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
Germany
State/province [8] 0 0
Haar
Country [9] 0 0
Israel
State/province [9] 0 0
Hod Hasharon
Country [10] 0 0
Italy
State/province [10] 0 0
Rome
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seoul
Country [12] 0 0
Mexico
State/province [12] 0 0
Mexico City
Country [13] 0 0
Netherlands
State/province [13] 0 0
Haarlem
Country [14] 0 0
Norway
State/province [14] 0 0
Drammen
Country [15] 0 0
Peru
State/province [15] 0 0
Lima
Country [16] 0 0
Philippines
State/province [16] 0 0
Makati
Country [17] 0 0
Poland
State/province [17] 0 0
Warsaw
Country [18] 0 0
Portugal
State/province [18] 0 0
Paco D'arcos
Country [19] 0 0
Russian Federation
State/province [19] 0 0
Moscow
Country [20] 0 0
South Africa
State/province [20] 0 0
Midrand
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Taiwan
State/province [22] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De... [More Details]