Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02132754




Registration number
NCT02132754
Ethics application status
Date submitted
5/05/2014
Date registered
7/05/2014
Date last updated
28/01/2021

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
MK-4166-001
Secondary ID [2] 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 0.0015 mg - Participant received 0.0015 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 0.0045 mg - Participant received 0.0045 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 0.014 mg - Participant received 0.014 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 0.04 mg - Participant received 0.04 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 0.12 mg - Participant received 0.12 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 0.37 mg - Participant received 0.37 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 1.1 mg - Participant received 1.1 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 3.3 mg - Participant received 3.3 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 10 mg - Participant received 10 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 30 mg - Participants received 30 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 42 mg - Participants received 42 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 59 mg - Participants received 59 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 82 mg - Participants received 82 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 120 mg - Participants received 120 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 170 mg - Participants received 170 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 240 mg - Participants received 240 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 340 mg - Participants received 340 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 480 mg - Participants received 480 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 670 mg - Participants received 670 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 900 mg - Participants received 900 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.

Experimental: MK-4166 1.1 mg + Pembro - Participants received 1.1 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 3.3 mg + Pembro - Participants received 3.3 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 10 mg + Pembro - Participants received 10 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 30 mg + Pembro - Participants received 30 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 42 mg + Pembro - Participants received 42 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 59 mg + Pembro - Participants received 59 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 82 mg + Pembro - Participants received 82 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 120 mg + Pembro - Participants received 120 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 170 mg + Pembro - Participants received 170 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 240 mg + Pembro - Participants received 240 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 340 mg + Pembro - Participants received 340 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 480 mg + Pembro - Participants received 480 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 670 mg + Pembro - Participants received 670 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.

Experimental: MK-4166 900 mg + Pembro - Participants received 900 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.


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)
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 90 days post last dose (up to 27 months)
Primary outcome [3] 0 0
Number of Participants Discontinuing Study Treatment Due to AEs
Timepoint [3] 0 0
Up to approximately 24 months
Secondary outcome [1] 0 0
Maximum Concentration (Cmax) of MK-4166 Over Time
Timepoint [1] 0 0
Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [2] 0 0
Time to Maximum Concentration (Tmax) of MK-4166 Over Time
Timepoint [2] 0 0
Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [3] 0 0
Terminal Half-Life (t ½) of MK-4166 Over Time
Timepoint [3] 0 0
Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [4] 0 0
Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time
Timepoint [4] 0 0
Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Day 2. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [5] 0 0
Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time
Timepoint [5] 0 0
Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [6] 0 0
Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time
Timepoint [6] 0 0
Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [7] 0 0
Apparent Clearance (CL) of MK-4166 Over Time
Timepoint [7] 0 0
Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [8] 0 0
Apparent Volume of Distribution (V) of MK-4166 Over Time
Timepoint [8] 0 0
Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [9] 0 0
Maximum Concentration (Cmax) of Pembrolizumab Over Time
Timepoint [9] 0 0
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [10] 0 0
Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time
Timepoint [10] 0 0
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [11] 0 0
Terminal Half-Life (t ½) of Pembrolizumab Over Time
Timepoint [11] 0 0
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [12] 0 0
Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time
Timepoint [12] 0 0
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Day 2. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [13] 0 0
Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time
Timepoint [13] 0 0
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [14] 0 0
Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time
Timepoint [14] 0 0
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [15] 0 0
Apparent Clearance (CL) of Pembrolizumab Over Time
Timepoint [15] 0 0
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [16] 0 0
Apparent Volume of Distribution (V) of Pembrolizumab Over Time
Timepoint [16] 0 0
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
Secondary outcome [17] 0 0
Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration
Timepoint [17] 0 0
Cycle 1 Day 1: at end of infusion (up to 10 minutes), 2 hours post-infusion, Cycle 1 Days 2, 3, 5, 8, 15, Cycle 2 Day 1 pre-dose. Each cycle was 21 days.

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
Sex
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/07/2019
Sample size
Target
Accrual to date
Final
116
Recruitment in Australia
Recruitment state(s)

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

Ethics approval
Ethics application status

Summary
Brief summary
This is planned to be a 5-part dose-escalation study to determine the safety and tolerability
of MK-4166 monotherapy and MK-4166 plus pembrolizumab combination therapy, and to establish
the maximum tolerated dose (MTD) or maximum administered dose (MAD) of MK-4166 and MK-4166
plus pembrolizumab by defining dose-limiting toxicities (DLTs) in participants with advanced
solid tumors.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02132754
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02132754