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

NCT03364049 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 7162-0022017-000418-49MK-7162-002
• Study Type: interventional
• Target: 33
• Locations: 4 countries
• Sites: 6

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.

Conditions

Solid Neoplasms

Outcome Measures

Primary Outcomes (3)

• 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.

  Cycle 1 and Cycle 2 (Up to 6 weeks)

• 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.

  Up to Approximately 27 Months

• 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.

  Up to Approximately 26 Months

Secondary Outcomes (7)

• Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab

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

• Minimum Plasma Concentration (Cmin) of MK-7162

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

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

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

• Kynurenine (KYN) Biomarker Plasma Concentration

  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

• Tryptophan (TRP) Biomarker Plasma Concentration

  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

Study Arms (4)

MK-7162 25 mg +Pembrolizumab (Pembro)

EXPERIMENTAL

Participants 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 \[Q3W\]).

Drug: MK-7162; Biological: Pembrolizumab

MK-7162 50 mg + Pembro

EXPERIMENTAL

Participants 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

Drug: MK-7162; Biological: Pembrolizumab

MK-7162 100 mg + Pembro

EXPERIMENTAL

Participants 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

Drug: MK-7162; Biological: Pembrolizumab

MK-7162 200 mg + Pembro

EXPERIMENTAL

Participants 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

Drug: MK-7162; Biological: Pembrolizumab

Interventions

MK-7162 DRUG

oral tablets

MK-7162 100 mg + Pembro; MK-7162 200 mg + Pembro; MK-7162 25 mg +Pembrolizumab (Pembro); MK-7162 50 mg + Pembro

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, Keytruda

MK-7162 100 mg + Pembro; MK-7162 200 mg + Pembro; MK-7162 25 mg +Pembrolizumab (Pembro); MK-7162 50 mg + Pembro

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (6)

UCLA Medical Center ( Site 0002)

Santa Monica, California, 90404, United States

Location

START Midwest ( Site 0007)

Grand Rapids, Michigan, 49546, United States

Location

Laura and Isaac Perlmutter Cancer Center ( Site 0001)

New York, New York, 10016, United States

Location

Princess Margaret Hospital.. ( Site 0130)

Toronto, Ontario, M5G 2M9, Canada

Location

Chaim Sheba Medical Center. ( Site 0301)

Ramat Gan, 5265601, Israel

Location

Severance Hospital Yonsei University Health System ( Site 0103)

Seoul, 03722, South Korea

Location

MeSH Terms

Interventions

pembrolizumab

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

18006726372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 6, 2017
• Study Start: December 6, 2017
• Primary Completion: October 19, 2020
• Study Completion: October 19, 2020
• Last Updated: November 15, 2021
• Results First Posted: November 15, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (3); IL (1); KR (1)