A Phase I/Ib Open-label, Multicenter Clinical Study of MK-0472 as Monotherapy and Combination Therapy in Participants With Advanced/Metastatic Solid Tumors.
Study Identifier:
MK-0472-001
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruitment Complete
Considering participating in a START clinical trial?
Study 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. There is no primary hypothesis to be tested for this study.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Bladder
Breast Cancers
Bowel (Colorectal)
Non-Small Cell Lung Cancer
Melanoma
Small Cell Lung
Renal
Gastric
Liver
Head & Neck
Solid Tumor
Mesothelioma
Endometrial
Digestive & Intestinal
Cervical cancer
Neuroendocrine
Squamous Cell Carcinoma
Anal
Bile Duct
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: MK-0472 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 Oral Administration Experimental: MK-0472 + Pembrolizumab 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 Oral Administration Biological: Pembrolizumab IV infusion Experimental: MK-0472 + MK-1084 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 Oral Administration Drug: MK-1084 Oral Administration
Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
Inclusion criteria
- The main inclusion criteria include but are not limited to the following:
- Has histologically or cytologically confirmed solid tumor by pathology report that is advanced/metastaticParticipants 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 enrollmentParticipants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screeningParticipants 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 benefitArm 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 mesotheliomaArm 3: Has histologically OR blood-based confirmation of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation
Exclusion criteria
- 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 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
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.
Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Irene Moreno
Maria de Miguel
Status
Recruitment Complete
Condition(s) Treated at Site
Bladder
Breast Cancers
Bowel (Colorectal)
Non-Small Cell Lung Cancer
Melanoma
Small Cell Lung
Renal
Gastric
Liver
Head & Neck
Solid Tumor
Mesothelioma
Endometrial
Digestive & Intestinal
Cervical cancer
Neuroendocrine
Squamous Cell Carcinoma
Anal
Bile Duct