Study of MK-0472 in Participants With Advanced/Metastatic Solid Tumors (MK-0472-001)

Advanced Solid Tumors Clinical Trial

Official title:

A Phase 1/1b Open-label, Multicenter Clinical Study of MK-0472 as Monotherapy and Combination Therapy in Participants With Advanced/Metastatic Solid Tumors.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05853367
• Other study ID #: 0472-001
• Secondary ID: MK-0472-001
• Status: Recruiting
• Phase: Phase 1
• Start date: July 6, 2023
• Est. completion date: February 12, 2028

Study information

• Verified date: September 2023
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy, safety, and tolerability of MK-0472 administered as monotherapy and in combination with pembrolizumab (MK-3475) in participants with histologically or cytologically confirmed diagnosis of advanced/metastatic solid tumors. There is no primary hypothesis to be tested for this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: February 12, 2028
• Est. primary completion date: February 12, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report with oncogenic receptor tyrosine kinase (RTK) pathway alterations confirmed by a historical report or local testing and have received, or been intolerant to, all available treatment known to confer clinical benefit
• Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
• Participants with human immunodeficiency virus (HIV) infection must have well controlled HIV on stable (>4 weeks) antiretroviral therapy (ART) Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• Has not recovered to common terminology criteria for adverse events (CTCAE) Grade 1 or better from any adverse events that were due to cancer therapeutics administered more than 4 weeks earlier. Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study
• Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• History of hyperparathyroidism or hypercalcemia
• Has one or more of the following ophthalmological findings/conditions: a) Intraocular pressure >21 mm Hg and/or any diagnosis of glaucoma b) Diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion and c) Diagnosis of retinal degenerative disease
• Has clinically significant cardiovascular disease
• Bullous exfoliative skin disorders of any grade
• Known hypersensitivity to MK-0472 or pembrolizumab, or any of their excipients
• Received therapy with a proton-pump inhibitor or an H2 histamine blocker receptor antagonist within 7 days before the first scheduled day of study dosing
• Has discontinued prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor due to an adverse event
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before first dose
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
• Has known additional malignancy that is progressing or has required active treatment within the past 2 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention
• Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
• Has history of pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has active infection requiring systemic therapy
• Has history of allogeneic tissue/solid organ transplant
• Have not adequately recovered from major surgery or have ongoing surgical complications

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• MK-0472
Oral Administration

Biological:
• Pembrolizumab
IV infusion

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Université de Montréal-Unit for Innovative Therapies ( Site 0100)	Montréal	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0101)	Toronto	Ontario
Switzerland	Ospedale Regionale Bellinzona e Valli ( Site 0200)	Bellinzona	Ticino
Switzerland	Hôpitaux Universitaires de Genève (HUG) ( Site 0202)	Genève	Geneve
Switzerland	Cantonal Hospital St.Gallen-Oncology & Hematology ( Site 0201)	st.Gallen	Sankt Gallen
United States	Northwestern Memorial Hospital ( Site 0002)	Chicago	Illinois
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 0001)	Hackensack	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experience a Dose Limiting Toxicity (DLT) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0	DLT will be defined as any drug-related AE observed during the DLT evaluation period (e.g. Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle.	At the end of Cycle 1 (each cycle is 21 days)
Primary	Number of Participants Who Experience One or More Adverse Events (AEs)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience one or more AE's will be reported.	Up to approximately 56 months
Primary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be reported.	Up to approximately 56 months
Secondary	Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of MK-0472	Blood samples will be collected at specified intervals for the determination of AUC0-t. AUC0-t is defined as the area under concentration-time curve from 0 to last quantifiable concentration.	Cycle 1 Day 1; Cycle 2 Day 1: Predose and 1, 2, 4, and 8 hours postdose; Cycles 1, 2: Days 2, 15: Predose (Each cycle length = 21 days)
Secondary	Lowest Plasma Concentration (Ctrough) of MK-0472	Blood samples will be collected at specified intervals for the determination of Ctrough. Ctrough is defined as the lowest concentration of MK-0472 reached before the next dose is administered.	Cycles 2-6, and every third cycle up to Cycle 81: Day 1: Predose (Each cycle length = 21 days)
Secondary	Maximum Serum Concentration (Cmax) of MK-0472	Blood samples will be collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-0472 reached.	Cycle 1 Day 1; Cycle 2 Day 1: 1, 2, 4, and 8 hours postdose (Each cycle length = 21 days)

External Links

•   Merck Clinical Trials Information