Metastatic Solid Tumors, Advanced Solid Tumors
Conditions
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)
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.
Interventions
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/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
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience a Dose Limiting Toxicity (DLT) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | At the end of Cycle 1 (each cycle is 21 days) | 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. |
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 56 months | 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. |
| Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | Up to approximately 56 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Blood samples will be collected at specified intervals for the determination of AUCtau. AUCtau is defined as the area under concentration-time curve from 0 to the end of the dosing period. |
| Lowest Plasma Concentration (Ctrough) of MK-0472 | At predetermined timepoints Predose up to Cycle 6 (Each cycle length = 21 Days) | 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. |
| Maximum Plasma Concentration (Cmax) of MK-0472 | At predetermined timepoints postdose up to Cycle 6 (Each cycle length = 21 Days) | Blood samples will be collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-0472 reached. |
Countries
Canada, Chile, Israel, Poland, Spain, Switzerland, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed