Clinical trial NCT03364049: Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002)
Official title: Phase 1b Open-label Study of MK-7162 in Combination With Pembrolizumab (MK-3475) +/- Other Therapies in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Neoplasms
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-12-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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 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.
* 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.

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 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.

Primary outcomes:
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
timeFrame: Cycle 1 and Cycle 2 (Up to 6 weeks)
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to Approximately 27 Months
measure: Number of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to Approximately 26 Months
Secondary outcomes:
measure: Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab
timeFrame: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 & 15; and Cycle 3, Day 1
measure: Minimum Plasma Concentration (Cmin) of MK-7162
timeFrame: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Day 14
measure: Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab
timeFrame: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 and 15 and Cycle 3, Day 1
measure: Kynurenine (KYN) Biomarker Plasma Concentration
timeFrame: 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
measure: Tryptophan (TRP) Biomarker Plasma Concentration
timeFrame: 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
measure: Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator
timeFrame: Up to approximately 28 months
measure: Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors
timeFrame: Up to approximately 28 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Medical Center ( Site 0002)
state: California
city: Grand Rapids
country: United States
facility: START Midwest ( Site 0007)
state: Michigan
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center ( Site 0001)
state: New York
city: Toronto
country: Canada
facility: Princess Margaret Hospital.. ( Site 0130)
state: Ontario
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center. ( Site 0301)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 0103)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: