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

NCT05853367 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: 0472-001MK-0472-0012024-516006-32-00U1111-1310-1179
• Study Type: interventional
• Target: 178
• Locations: 7 countries
• Sites: 25

Brief 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) or MK-1084 in participants with histologically or cytologically confirmed diagnosis of advanced/metastatic solid tumors.

Conditions

Metastatic Solid Tumors; Advanced Solid Tumors

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (SHP-2)

Outcome Measures

Primary Outcomes (3)

• 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)

• 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

• 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 Outcomes (3)

• Area Under the Concentration Time-curve From Time 0 to the End of the Dosing Period (AUCtau) of MK-0472

  At predetermined timepoints predose and postdose up to Cycle 6 (Each cycle length = 21 Days)

• Lowest Plasma Concentration (Ctrough) of MK-0472

  At predetermined timepoints Predose up to Cycle 6 (Each cycle length = 21 Days)

• Maximum Plasma Concentration (Cmax) of MK-0472

  At predetermined timepoints postdose up to Cycle 6 (Each cycle length = 21 Days)

Study Arms (3)

MK-0472

EXPERIMENTAL

Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens until disease progression or withdrawal/discontinuation.

Drug: MK-0472

MK-0472 + Pembrolizumab

EXPERIMENTAL

Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens until disease progression or withdrawal/discontinuation, plus pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Drug: MK-0472; Biological: Pembrolizumab

MK-0472 + MK-1084

EXPERIMENTAL

Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens, plus MK-1084 via oral capsule until disease progression or withdrawal/discontinuation.

Drug: MK-0472; Drug: MK-1084

Interventions

MK-0472 DRUG

Oral Administration

MK-0472; MK-0472 + MK-1084; MK-0472 + Pembrolizumab

MK-1084 DRUG

Oral Administration

MK-0472 + MK-1084

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, Keytruda®

MK-0472 + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Has histologically or cytologically confirmed solid tumor by pathology report that is advanced/metastatic
• 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 study enrollment
• 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)
• Arm 1: Oncogenic receptor tyrosine kinase (RTK) pathway alterations confirmed by a historical report or local testing (tissue or blood) and have received, or been intolerant to, all available treatment known to confer clinical benefit
• Arm 2: Tumor types known to be sensitive to anti-programmed cell death 1 protein (PD-1)/ligand 1 (L1) therapies are eligible. Tumor types permitted include: melanoma, non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/ROS1 mutations, renal cell carcinoma, urothelial carcinoma, Merkel cell carcinoma, MSI-high CRC, endometrial cancer, cervical cancer, small cell lung cancer, triple negative breast cancer, esophageal cancer, gastric cancer, biliary tract cancer, hepatocellular carcinoma, head and neck squamous cancer, cutaneous squamous cancer, anal squamous cancer, and mesothelioma
• Arm 3: Has histologically OR blood-based confirmation of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation

You may not qualify if:

• 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, MK-1084, 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (25)

Northwestern Memorial Hospital ( Site 0002)

Chicago, Illinois, 60611, United States

RECRUITING

The University of Louisville, James Graham Brown Cancer Center ( Site 0004)

Louisville, Kentucky, 40202, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0001)

Hackensack, New Jersey, 07601, United States

RECRUITING

Rutgers Cancer Institute of New Jersey ( Site 0005)

New Brunswick, New Jersey, 08901, United States

RECRUITING

Princess Margaret Cancer Centre ( Site 0101)

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Centre Hospitalier de l'Université de Montréal-Unit for Innovative Therapies ( Site 0100)

Montreal, Quebec, H2X 0A9, Canada

RECRUITING

Jewish General Hospital ( Site 0104)

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Centro de Estudios Clínicos SAGA ( Site 0701)

Santiago, Region M. de Santiago, 7500653, Chile

RECRUITING

Fundacion Arturo Lopez Perez ( Site 0700)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Centro de Investigacion Clinicadela Universidad Catolica ( Site 0703)

Santiago, Region M. de Santiago, 8330034, Chile

RECRUITING

Bradfordhill ( Site 0702)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

Rambam Health Care Campus ( Site 0304)

Haifa, 3109601, Israel

RECRUITING

Shaare Zedek Medical Center ( Site 0303)

Jerusalem, 9103102, Israel

RECRUITING

Rabin Medical Center ( Site 0301)

Petah Tikva, 4941492, Israel

RECRUITING

Sheba Medical Center ( Site 0300)

Ramat Gan, 5265601, Israel

RECRUITING

Sourasky Medical Center ( Site 0302)

Tel Aviv, 6423906, Israel

RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 0401)

Warsaw, Masovian Voivodeship, 02-781, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne ( Site 0400)

Gdansk, Pomeranian Voivodeship, 80-214, Poland

RECRUITING

Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 0501)

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

RECRUITING

Centro Integral Oncologico Clara Campal-Hospital HM Universitario Sanchinarro-START Madrid, ( Site 0504)

Madrid, Madrid, Comunidad de, 28050, Spain

RECRUITING

Hospital Universitari Vall d'Hebron ( Site 0500)

Barcelona, 08035, Spain

RECRUITING

Hospital Virgen del Rocio ( Site 0503)

Seville, 41013, Spain

RECRUITING

Hôpitaux Universitaires de Genève (HUG) ( Site 0202)

Geneva, Canton of Geneva, 1211, Switzerland

RECRUITING

Cantonal Hospital St.Gallen-Oncology & Hematology ( Site 0201)

Sankt Gallen, Canton of St. Gallen, 9000, Switzerland

RECRUITING

Ospedale Regionale Bellinzona e Valli ( Site 0200)

Bellinzona, Canton Ticino, 6500, Switzerland

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: May 10, 2023
• Study Start: July 6, 2023
• Primary Completion (Estimated): February 12, 2028
• Study Completion (Estimated): February 12, 2028
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

ES (4); CH (3); CA (3); US (4); CL (4); IL (5); PL (2)