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

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ClinicalTrials.gov Identifier: NCT03364049
Recruitment Status : Recruiting
First Posted : December 6, 2017
Last Update Posted : July 4, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
The purposes of this study are to: 1) determine the safety and tolerability of MK-7162 when administered in combination with pembrolizumab (MK-3475), 2) establish a preliminary recommended Phase 2 dose (RP2D) of MK-7162 when administered in combination with pembrolizumab, and 3) assess the pharmacokinetics and pharmacodynamics of MK-7162 when administered in combination with pembrolizumab and other therapies to adult participants with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Solid Neoplasms Drug: MK-7162 Biological: Pembrolizumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b Open-label Study of MK-7162 in Combination With Pembrolizumab (MK-3475) +/- Other Therapies in Participants With Advanced Solid Tumors
Actual Study Start Date : December 6, 2017
Estimated Primary Completion Date : January 13, 2021
Estimated Study Completion Date : January 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MK-7162+Pembrolizumab
Cycle 1: Participants receive MK-7162 (at a daily dose of between 25 mg and 400 mg) via oral tablets once daily (QD) throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 (at a daily dose of between 25 mg and 400 mg) via oral tablets QD PLUS pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (every 3 weeks [Q3W]).
Drug: MK-7162
oral tablets

Biological: Pembrolizumab
IV infusion
Other Name: MK-3475




Primary Outcome Measures :
  1. 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 following events, if considered drug related by the Investigator, will be 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 AEs ≥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. The number of participants who experience a DLT will be presented.

  2. Adverse Events (AEs) [ Time Frame: Up to approximately 26 months (Through 30 days after last dose of study treatment) ]
    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. The number of participants who experience an AE will be presented.

  3. Discontinuations of Study Treatment Due to an AE [ Time Frame: Up to approximately 25 months (Through last dose of study treatment) ]
    The number of participants who discontinue study treatment due to an AE will be presented.


Secondary Outcome Measures :
  1. MK-7162 Area Under the Concentration-Time Curve (AUC) When Administered Alone and in Combination with Pembrolizumab [ Time Frame: Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Days 1 & 15: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose; Cycles 4 through 36 Day 1: predose every 4 cycles (Up to approximately 25 months) ]
    Blood draws will be obtained at designated time points. The AUC of MK-7162 when administered alone and in combination with pembrolizumab will be presented.

  2. MK-7162 Minimum Observed Concentration (Cmin) When Administered Alone and in Combination with Pembrolizumab [ Time Frame: Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Days 1 & 15: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose; Cycles 4 through 36 Day 1: predose every 4 cycles (Up to approximately 25 months) ]
    Blood draws will be obtained at designated time points. The Cmin of MK-7162 when administered alone and in combination with pembrolizumab will be presented.

  3. MK-7162 Maximum Observed Concentration (Cmax) When Administered Alone and in Combination with Pembrolizumab [ Time Frame: Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Days 1 & 15: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose; Cycles 4 through 36 Day 1: predose every 4 cycles (Up to approximately 25 months) ]
    Blood draws will be obtained at designated time points. The Cmax of MK-7162 when administered alone and in combination with pembrolizumab will be presented.

  4. Ratio of Kynurenine (KYN):Tryptophan (TRP) Biomarker Plasma Concentrations [ Time Frame: Screening; 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 (Up to approximately 9 weeks) ]
    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 will be collected after an overnight fast for measurement of plasma levels of KYN and TRP as a progressive disease (PD) biomarker of IDO1 inhibition. The ratio of KYN:TRP will be calculated at designated time points. A reduction (negative change from baseline) in KYN:TRP plasma concentration is indicative of a reduction in IDO1 activity.

  5. Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator [ Time Frame: Up to approximately 25 months ]
    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.

  6. ORR Based on Immune-related RECIST (irRECIST) as Assessed by the Investigator [ Time Frame: Up to approximately 25 months ]
    For participants with radiological PD by RECIST 1.1 as determined by the Investigator, will undergo confirmatory imaging which will classify participant disease as confirmed progressive disease [iCPD]), or as unconfirmed progressive disease [iUPD]), or as disease stability or response (stable disease [iSD]/partial response [iPR]/confirmed response [iCR]). iCPD definition: Target lesions, worsening is a further increase in the sum of diameters of ≥5 mm; Non-target lesions, worsening is any significant growth in lesions overall; New lesions, worsening is any of these: an increase in new lesion sum of diameters by ≥5 mm; Visible growth of new non-target lesions; Appearance of additional new lesions; or any new factor appears 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. The percentage of participants who experience iSD, iPR or iCR will be presented.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 measureable 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.
  • 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 agrees to use contraception during the treatment period and for ≥120 days after last dose of study treatment.

Exclusion Criteria:

  • 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.
  • 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 an monoamine oxidase-inhibitors (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03364049


Contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
United States, California
UCLA Medical Center ( Site 0002) Recruiting
Santa Monica, California, United States, 90404
Contact: Study Coordinator    310-829-5471      
United States, Michigan
START Midwest ( Site 0007) Recruiting
Grand Rapids, Michigan, United States, 49546
Contact: Study Coordinator    616-954-5551      
United States, New York
Laura and Isaac Perlmutter Cancer Center ( Site 0001) Recruiting
New York, New York, United States, 10016
Contact: Study Coordinator    212-731-5445      
Canada, Ontario
Princess Margaret Hospital ( Site 0130) Recruiting
Toronto, Ontario, Canada, M5G 1X6
Contact: Study Coordinator    4169462911      
Israel
Chaim Sheba Medical Center. ( Site 0301) Recruiting
Ramat-Gan, Israel, 5265601
Contact: Study Coordinator    +97235302542      
Korea, Republic of
Severance Hospital Yonsei University Health System ( Site 0103) Recruiting
Seoul, Korea, Republic of, 03722
Contact: Study Coordinator    +82222288132      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03364049     History of Changes
Other Study ID Numbers: 7162-002
2017-000418-49 ( EudraCT Number )
MK-7162-002 ( Other Identifier: Merck Protocol Number )
First Posted: December 6, 2017    Key Record Dates
Last Update Posted: July 4, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Pembrolizumab
Antineoplastic Agents