Study of MK-4166 and MK-4166 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4166-001)
Phase 1 Trial of Single Agent MK-4166 and MK-4166 in Combination With Pembrolizumab in Subjects With Advanced Malignancies
2 other identifiers
interventional
116
0 countries
N/A
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2014
Longer than P75 for phase_1
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 5, 2014
CompletedFirst Posted
Study publicly available on registry
May 7, 2014
CompletedStudy Start
First participant enrolled
June 27, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
July 31, 2019
CompletedResults Posted
Study results publicly available
July 31, 2020
CompletedJanuary 28, 2021
January 1, 2021
5.1 years
May 5, 2014
July 13, 2020
January 12, 2021
Conditions
Outcome Measures
Primary Outcomes (3)
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
DLT's were assessed during the first cycle (21 days) for each dose level and included the following if assessed by the Investigator to be possibly, probably or definitely related to MK-4166 or MK-4166 plus pembrolizumab combination: Grade 4 non-hematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia (Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia if associated with bleeding); Grade 3 non-hematologic toxicity lasting \>3 days despite optimal supportive care; Grade 3 nausea, vomiting or diarrhea if \>3 days despite optimal supportive care; any Grade 3 or Grade 4 non-hematologic laboratory abnormality if medical intervention is required or if leading to hospitalization or if persisting for \>1 week; febrile neutropenia Grade 3 or Grade 4; any drug-related AE which caused participant to discontinue treatment during Cycle 1; Grade 5 toxicity; any treatment-related toxicity which caused a \>2 week delay in initiation of Cycle 2.
Cycle 1 (up to 21 days)
Number of Participants Experiencing Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants experiencing an AE was assessed and reported by arm (MK-4166 monotherapy and MK-4166 plus pembrolizumab combination therapy) as well as by dose cohort.
From first dose up to 90 days post last dose (up to 27 months)
Number of Participants Discontinuing Study Treatment Due to AEs
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants discontinuing study treatment due to AEs was assessed and reported by arm (MK-4166 monotherapy and MK-4166 plus pembrolizumab combination therapy) as well as by dose cohort.
Up to approximately 24 months
Secondary Outcomes (17)
Maximum Concentration (Cmax) of MK-4166 Over Time
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)
Time to Maximum Concentration (Tmax) of MK-4166 Over Time
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)
Terminal Half-Life (t ½) of MK-4166 Over Time
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)
Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time
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)
Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time
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)
- +12 more secondary outcomes
Study Arms (34)
MK-4166 0.0015 mg
EXPERIMENTALParticipant received 0.0015 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 0.0045 mg
EXPERIMENTALParticipant received 0.0045 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 0.014 mg
EXPERIMENTALParticipant received 0.014 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 0.04 mg
EXPERIMENTALParticipant received 0.04 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 0.12 mg
EXPERIMENTALParticipant received 0.12 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 0.37 mg
EXPERIMENTALParticipant received 0.37 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 1.1 mg
EXPERIMENTALParticipant received 1.1 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 3.3 mg
EXPERIMENTALParticipant received 3.3 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 10 mg
EXPERIMENTALParticipant received 10 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 30 mg
EXPERIMENTALParticipants received 30 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 42 mg
EXPERIMENTALParticipants received 42 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 59 mg
EXPERIMENTALParticipants received 59 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 82 mg
EXPERIMENTALParticipants received 82 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 120 mg
EXPERIMENTALParticipants received 120 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 170 mg
EXPERIMENTALParticipants received 170 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 240 mg
EXPERIMENTALParticipants received 240 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 340 mg
EXPERIMENTALParticipants received 340 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 480 mg
EXPERIMENTALParticipants received 480 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 670 mg
EXPERIMENTALParticipants received 670 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 900 mg
EXPERIMENTALParticipants received 900 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
MK-4166 1.1 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 3.3 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 10 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 30 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 42 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 59 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 82 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 120 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 170 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 240 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 340 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 480 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 670 mg + Pembro
EXPERIMENTALParticipants 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.
MK-4166 900 mg + Pembro
EXPERIMENTALParticipants 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (1)
Papadopoulos KP, Autio K, Golan T, Dobrenkov K, Chartash E, Chen Q, Wnek R, Long GV. Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors. Clin Cancer Res. 2021 Apr 1;27(7):1904-1911. doi: 10.1158/1078-0432.CCR-20-2886. Epub 2020 Dec 21.
PMID: 33355238RESULT
MeSH Terms
Interventions
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme Corp.
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 5, 2014
First Posted
May 7, 2014
Study Start
June 27, 2014
Primary Completion
July 31, 2019
Study Completion
July 31, 2019
Last Updated
January 28, 2021
Results First Posted
July 31, 2020
Record last verified: 2021-01
Data Sharing
- IPD Sharing
- Will share
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf