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Solid NeoplasmsPhase 1NCT03364049

Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002)

A Phase 1 study testing MK-7162 and Pembrolizumab in people with Solid Neoplasms, run by Merck Sharp & Dohme LLC at 6 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purposes of this study are to determine the safety and tolerability of MK-7162 when administered in combination with pembrolizumab (MK-3475) and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-7162 when administered in combination with pembrolizumab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Neoplasms
What is being tested?
MK-7162 and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
6 sitesin 4 countries
Study dates
6 Dec 2017to 19 Oct 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, or been ineligible for all treatment known to confer clinical benefit. Participants with solid tumors of any type are eligible for enrollment.
  • Has stage III or stage IV disease that is not surgically resectable.
  • Has measurable disease by RECIST 1.1 criteria as assessed by the local site investigator/radiology.
  • Has 1 or more discrete malignant lesions that are amenable to ≥2 separate biopsies guided by one of the following modalities: visual inspection, ultrasound guidance, or cross sectional image guidance (computed tomography/magnetic resonance imaging [CT/MRI]).
  • Has an evaluable baseline tumor sample to submit for analysis.
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
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  • Demonstrates adequate organ function.
  • If male, must agree to use contraception and refrain from donating sperm during the treatment period and for ≥120 days after last dose of study treatment.
  • If female, is not pregnant or breastfeeding, and if a woman of childbearing potential (WOCCBP), agrees to use contraception during the treatment period and for ≥120 days after last dose of study treatment.

Who cannot join

  • Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. (Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers.)
  • Has a known active central nervous system metastasis and/or carcinomatous meningitis.
  • Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody/components of the study treatment(s).
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy.
  • Has a history of vasculitis.
  • Has an active infection requiring systemic therapy.
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  • Has symptomatic ascites or pleural effusion.
  • Has interstitial lung disease that has required oral or intravenous glucocorticoids to assist with management.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Note: Participants who have had a stem cell transplant >5 years ago are eligible as long as there are no symptoms of graft-versus-host disease [GVHD].)
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has known active Hepatitis B or known active Hepatitis C virus infection.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
  • Has not fully recovered from any effects of major surgery without significant detectable infection.
  • Has received prior systemic anti-cancer therapy including investigational agents or has used an investigational device within 28 days prior to the first dose of study treatment. (Notes: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Prior exposure to immunotherapeutics is allowed, including programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, provided the participant did not experience ≥Grade 3 drug-related toxicity on monotherapy with a PD-1 or PD-L1 inhibitor.
  • Has been previously treated with an Indoleamine-2,3-dioxygenase-1 (IDO1) inhibitor (e.g., epacadostat, BMS-986205)
  • Has received prior radiotherapy within 2 weeks of start of study treatment.
  • Is receiving a monoamine oxidase inhibitor (MAOI) or any drug which has significant MAOI activity (e.g., meperidine, linezolid, methylene blue) within the 21 days before screening, or has a history of Serotonin Syndrome after receiving serotonergic drugs.
  • Is expected to require any non-protocol antineoplastic therapy while on study.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in excess of replacement doses (the equivalent of prednisone ≤10 mg/day is acceptable), or on any other form of immunosuppressive medication.
  • Has received a live-virus vaccine within 30 days prior to first dose of study medication.

Trial locations and contacts

6 sites in 4 countries.

6 sites in 4 countries

United States3 sites
  • START Midwest ( Site 0007)

    Grand Rapids, Michigan, 49546

  • Laura and Isaac Perlmutter Cancer Center ( Site 0001)

    New York, New York, 10016

  • UCLA Medical Center ( Site 0002)

    Santa Monica, California, 90404

Other trials in United States

Canada1 site
  • Princess Margaret Hospital.. ( Site 0130)

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Israel1 site
  • Chaim Sheba Medical Center. ( Site 0301)

    Ramat Gan, 5265601

Other trials in Israel

South Korea1 site
  • Severance Hospital Yonsei University Health System ( Site 0103)

    Seoul, 03722

Other trials in South Korea

About this study

Official title: Phase 1b Open-label Study of MK-7162 in Combination With Pembrolizumab (MK-3475) +/- Other Therapies in Participants With Advanced Solid Tumors

The purposes of this study are to determine the safety and tolerability of MK-7162 when administered in combination with pembrolizumab (MK-3475) and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-7162 when administered in combination with pembrolizumab.

Conditions
Solid Neoplasms
Being tested
MK-7162, Pembrolizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-7162Drug

    oral tablets

  • PembrolizumabBiological

    Also called MK-3475, Keytruda

    IV infusion

Study groups in NCT03364049
Study groupRoleWhat they receive
MK-7162 25 mg +Pembrolizumab (Pembro)ExperimentalParticipants receive MK-7162 25 mg via oral tablets once daily (QD) throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 25 mg orally QD PLUS pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (every 3 weeks [Q3W]).
Receives: Drug: MK-7162; Biological: Pembrolizumab
MK-7162 50 mg + PembroExperimentalParticipants receive MK-7162 50 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-71625 50 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W
Receives: Drug: MK-7162; Biological: Pembrolizumab
MK-7162 100 mg + PembroExperimentalParticipants receive MK-7162 100 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 100 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W
Receives: Drug: MK-7162; Biological: Pembrolizumab
MK-7162 200 mg + PembroExperimentalParticipants receive MK-7162 200 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 200 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W
Receives: Drug: MK-7162; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator

    The following events, if considered drug related by the investigator, are considered a DLT: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia associated with bleeding; Nonhematologic Adverse Events (AE) ≥Grade 3 with exceptions; Grade 3 or Grade 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, persists for >1 week, or results in a Drug-induced Liver Injury with exceptions; Grade 3 of 4 febrile neutropenia; Treatment-related toxicities that lead to discontinuation of study treatment during Cycles 1 or 2; Prolonged delay (>2 weeks) in initiating Cycles 2 or 3 due to treatment-related toxicity; Missing >25% of MK-7162 doses as a result of treatment-related AE during Cycles 1 or 2; Grade 5 toxicity.

    Measured: Cycle 1 and Cycle 2 (Up to 6 weeks)

  2. Number of Participants Who Experienced an Adverse Event (AE)

    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.

    Measured: Up to Approximately 27 Months

  3. Number of Participants Who Discontinued Study Drug Due to an AE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

    Measured: Up to Approximately 26 Months

Secondary outcomes (7)
  1. Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab

    Blood samples were collected at designated time points for determining the AUC₀-₈ of MK-7162 in plasma when administered alone and in combination with pembrolizumab.

    Measured: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 & 15; and Cycle 3, Day 1

  2. Minimum Plasma Concentration (Cmin) of MK-7162

    Blood samples were obtained at designated time points to determine the Cmin of MK-7162 in plasma.

    Measured: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Day 14

  3. Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab

    Blood samples were collected at designated time points to determine the Cmax of MK-7162 in plasma when administered alone and in combination with pembrolizumab.

    Measured: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 and 15 and Cycle 3, Day 1

  4. Kynurenine (KYN) Biomarker Plasma Concentration

    MK-7162 is a selective inhibitor of Indoleamine-2,3-dioxygenase-1 (IDO1) activity which, in turn, reduces the conversion of TRP to KYN. Venous blood samples were collected after an overnight fast for measurement of plasma levels of KYN as a pharmacodynamic biomarker of IDO1 inhibition.

    Measured: Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Day 1: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose

  5. Tryptophan (TRP) Biomarker Plasma Concentration

    MK-7162 is a selective inhibitor of Indoleamine-2,3-dioxygenase-1 (IDO1) activity which, in turn, reduces the conversion of TRP to KYN. Venous blood samples were collected at designated time points after an overnight fast for measurement of plasma levels of TRP as a pharmacodynamic biomarker of IDO1 inhibition.

    Measured: Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Day 1: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose

  6. Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator

    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by the Investigator. The percentage of participants who experience a CR or PR based on RECIST 1.1 will be presented.

    Measured: Up to approximately 28 months

  7. Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors

    Participants with PD by RECIST 1.1 as determined by investigator underwent confirmatory imaging to classify the disease as confirmed progressive disease (iCPD), unconfirmed progressive disease [iUPD]), stable disease (iSD), partial response (iPR) or complete response (iCR). iCPD definition: Worsening of target lesions (increase in the sum of diameters of ≥5 mm); Any significant growth in non-target lesions, Appearance of new lesions, increase in new lesion sum of diameters by ≥5 mm; Visible growth of new non-target lesions; or appearance of new factor that would have triggered PD by RECIST 1.1. Responses are classified as iSD or iPR (depending on the sum of diameters of the target lesions), or iCR if all lesions resolve. iUPD overall response is defined as none of the progression-confirming factors identified in iCPD occurs AND The target lesion sum of diameters (initial target lesions) remains above the initial PD threshold (by RECIST 1.1)

    Measured: Up to approximately 28 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2017
  2. Study start6 Dec 2017
  3. Primary completion19 Oct 2020
  4. Study completion19 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03364049
Sponsor's protocol ID
7162-002
Other IDs
2017-000418-49, MK-7162-002, 2017
Status last verified
Nov 2021
First submitted
30 Nov 2017
Last updated
15 Nov 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-7162 and Pembrolizumab in people with Solid Neoplasms, run by Merck Sharp & Dohme LLC at 6 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, Canada, Israel, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator (time frame: Cycle 1 and Cycle 2 (Up to 6 weeks)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2021.

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