Study of MK-4166 and MK-4166 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4166-001)

NCT ID: NCT02132754

Last Updated: 2021-01-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

116 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-27

Study Completion Date

2019-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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 C will be removed and the dose confirmation Part E (combination of MK-4166 and pembrolizumab) will be limited to participants with advanced malignant melanoma.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Solid Tumor

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 10 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 30 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 42 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 59 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 82 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 120 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 170 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 240 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 340 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 480 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 670 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

MK-4166 900 mg

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

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

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.

Group Type EXPERIMENTAL

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

MK-4166

Intervention Type BIOLOGICAL

Pembrolizumab

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type RESULT
PMID: 33355238 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

MK-4166-001

Identifier Type: OTHER

Identifier Source: secondary_id

4166-001

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.