Clinical trial NCT05514444: Study of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors (MK-4464-001)
Official title: A Phase 1, Open-label, Multicenter Study of the Safety, Pharmacokinetics, and Pharmacodynamics of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced/Metastatic Solid Tumors
Neoplasms
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-08-24
Enrollment: 260
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 purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of MK-4464 as monotherapy and in combination with pembrolizumab in participants with advanced/metastatic solid tumors.


Eligibility criteria: Inclusion Criteria:

The key Inclusion Criteria include but are not limited to the following:

* Have a histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit
* Must submit a baseline tumor sample for analysis
* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
* Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART)
* Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before randomization.

Exclusion Criteria:

The key Exclusion Criteria include but are not limited to the following:

* Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention or has not recovered to CTCAE Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
* Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active infection requiring therapy
* History of an allogenic stem cell transplant or a solid organ transplant
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has an active autoimmune disease that has required systemic treatment in the past 2 years
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study
* Has not fully recovered from any effects of major surgery without significant detectable infection
* Has received radiation therapy to the lung that is \>30 gray (Gy) within 6 months of the first dose of study treatment
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 28 days

Primary outcomes:
measure: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
timeFrame: Up to approximately 21 days
measure: Number of Participants Who Experience At Least One adverse event (AE)
timeFrame: Up to approximately 27 months
measure: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Minimum Plasma Concentration (Cmin) of MK-4464
timeFrame: Once daily on Day 2, 3, 5, 8, 15 of Cycle 1 and 4, Pre-dose and immediately Post-dose Day 1 Cycle 1, 2, 3, 4, Pre-dose Day 1 Cycles 5, 6, 7, 8, and every 4 cycles thereafter through Cycle 35, 30 days post last dose (up to ~25 months); Cycle = 21 days
measure: Maximum Plasma Concentration (Cmax) of MK-4464
timeFrame: Once daily on Day 2, 3, 5, 8, 15 of Cycle 1 and 4, Pre-dose and immediately Post-dose Day 1 Cycle 1, 2, 3, 4, Pre-dose Day 1 Cycles 5, 6, 7, 8, and every 4 cycles thereafter through Cycle 35, 30 days post last dose (up to ~25 months); Cycle = 21 days
measure: Area Under the Plasma Concentration-Time Curve (AUC) of MK-4464
timeFrame: Once daily on Day 2, 3, 5, 8, 15 of Cycle 1 and 4, Pre-dose and immediately Post-dose Day 1 Cycle 1, 2, 3, 4, Pre-dose Day 1 Cycles 5, 6, 7, 8, and every 4 cycles thereafter through Cycle 35, 30 days post last dose (up to ~25 months); Cycle = 21 days
measure: Objective Response Rate (ORR)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Louisville
country: United States
facility: The University of Louisville, James Graham Brown Cancer Center ( Site 0100)
state: Kentucky
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0201)
state: Ontario
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology Division ( Site 0300)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Oncology ( Site 0302)
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut - Antoni van Leeuwenhoek - NKI-AVL ( Site 0401)
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie VUmc ( Site 0400)
state: Noord-Holland
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: