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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02132754




Registration number
NCT02132754
Ethics application status
Date submitted
5/05/2014
Date registered
5/05/2014
Date last updated
13/06/2018

Titles & IDs
Public title
Study of MK-4166 and MK-4166 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4166-001)
Scientific title
Phase 1 Trial of Single Agent MK-4166 and MK-4166 in Combination With Pembrolizumab in Subjects With Advanced Malignancies
Secondary ID [1] 0 0
4166-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MK-4166
Other interventions - Pembrolizumab

Experimental: MK-4166 - Participants receive MK-4166 at assigned dose, intravenously over 30 minutes, on Day 1 of each 21-day cycle, for up to 4 cycles.

Experimental: MK-4166+Pembrolizumab - Participants receive MK-4166 at assigned dose, intravenously over 30 minutes on Day 1 of each 21-day cycle for up to 4 cycles and receive pembrolizumab 200 mg, intravenously over 30 minutes on Day 1 of each 21-day cycle for up to 24 months.


Other interventions: MK-4166


Other interventions: Pembrolizumab


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

Outcomes
Primary outcome [1] 0 0
Number of participants experiencing dose-limiting toxicities (DLTs) with MK-4166 and with MK-4166+Pembrolizumab
Timepoint [1] 0 0
Cycle 1 (up to 21 days)
Primary outcome [2] 0 0
Number of participants experiencing adverse events (AEs)
Timepoint [2] 0 0
From first dose up to 30 days post last dose (up to 25 months)
Primary outcome [3] 0 0
Number of participants discontinuing study drug due to AEs
Timepoint [3] 0 0
Up to 24 months

Eligibility
Key inclusion criteria
Inclusion criteria:

- Has a histologically- or cytologically-confirmed metastatic solid tumor for which
there is no available therapy which may convey clinical benefit. Part E: Has advanced
malignant melanoma.

- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version
1.1

- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale

- Adequate organ function

- Female participants of childbearing potential must have a negative urine or serum
pregnancy test and must be surgically sterile or willing to use 2 methods of birth
control or abstain from heterosexual activity for the course of the study through 120
days after last dose of study drug

- Male participants must agree to use an adequate method of contraception during sexual
contact with females of childbearing potential starting with the first dose of study
drug through 180 days after the last dose of study drug

- Submit an evaluable tumor sample for analysis.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the
first dose of study drug, or who has not recovered to Common Terminology Criteria for
Adverse Events (CTCAE) Grade 1 or better from the adverse events due to cancer
therapeutics administered more than 4 weeks earlier

- Currently participating or has participated in a study of an investigational agent or
using an investigational device within 28 days of administration of MK-4166

- Expected to require any other form of antineoplastic therapy while on study

- On chronic systemic steroid therapy in excess of replacement doses, or on any other
form of immunosuppressive medication

- History of a malignancy for which potentially curative treatment has been completed,
with no evidence of malignancy for 5 years excepting successful definitive resection
of basal cell carcinoma of the skin, superficial bladder cancer, or in situ cervical
cancer

- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

- Severe hypersensitivity reaction to treatment with another monoclonal antibody

- Active autoimmune disease or a documented history of autoimmune disease, except
vitiligo or resolved childhood asthma/atopy

- Active infection requiring therapy

- Current pneumonitis, or a history of (non-infectious) pneumonitis that required
steroids

- Prior stem cell or bone marrow transplant

- Positive for human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C

- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial

- Regular user (including "recreational use") of any illicit drugs or recent history
(within the last year) of substance abuse (including alcohol)

- Symptomatic ascites or pleural effusion

- Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the study

- Clinically significant heart disease

- Major surgery in the past 16 weeks

- Received a live vaccine within 30 days prior to first dose of study drug

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 1
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
Merck Sharp & Dohme - 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
Texas
Country [2] 0 0
Israel
State/province [2] 0 0
Hod Hasharon

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a 5-part dose-escalation study to determine the maximum tolerated dose (MTD)/maximum
administered dose (MAD) of MK-4166 in participants with advanced solid tumors. In Part A,
MK-4166 doses will be escalated quickly in successive cohorts and based on safety events may
progress to Part B, in which the preliminary MTD will be identified. Based on safety events
the study may progress to Part C in which the MTD will be confirmed. In Part D, participants
will receive escalating doses of MK-4166 plus a fixed dose of pembrolizumab (MK-3475) 200 mg
to determine the MTD for MK-4166 in combination with pembrolizumab. Based on safety events in
Part D, the study may progress to Part E in which the MTD for MK-4166 in combination with
pembrolizumab will be confirmed.

With Amendments 05/06, the dose confirmation Part E (combination of MK-4166 and
pembrolizumab) will be limited to participants with advanced malignant melanoma.

The primary study hypotheses are that MK-4166 as a single agent and MK-4166 in combination
with pembrolizumab have acceptable safety and tolerability.
Trial website
https://clinicaltrials.gov/show/NCT02132754
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02132754