Malignant Neoplam, Advanced Solid Tumors
Conditions
Brief summary
Researchers are looking for new ways to treat certain types of advanced solid tumors. Solid tumors are cancers mostly in organs and tissues in the body, not in the blood or other fluids. Advanced means the cancer has spread nearby or to other parts in the body and cannot be removed with surgery. In this trial, researchers want to learn if the trial medicine called MK-2010, given alone or with other treatments, can treat advanced solid tumors. MK-2010 is designed to help the immune system fight cancer. The goals of this trial are to learn: * About the safety of MK-2010 as monotherapy and in combinations and if participants tolerate them. Tolerate means participants will receive trial treatment unless they need to stop it due to health problems. * How many participants who receive MK-2010 as monotherapy and in combination respond to treatment. Respond means the cancer gets smaller or goes away.
Interventions
BIOLOGICALMK-2010
Administered as an intravenous (IV) infusion.
BIOLOGICALPembrolizumab
Administered intravenously as 400 mg every 6 weeks.
DRUG5-Fluorouracil
Administered intravenously per approved product label.
Administered intravenously per approved product label.
DRUGOxaliplatin
Administered intravenously per approved product label.
DRUGBelzutifan
Administered orally as 120 mg daily.
DRUGGemcitabine
Administered intravenously per approved product label.
DRUGCisplatin
Administered intravenously per approved product label.
DRUGCarboplatin
Administered intravenously per approved product label.
DRUGPaclitaxel
Administered intravenously per approved product label.
DRUGNab-paclitaxel
Administered intravenously per approved product label.
DRUGPemetrexed
Administered intravenously per approved product label.
DRUGEpinephrine
Administered per approved product label as rescue medication.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
For the MK-2010 + FOLFOX and Pembrolizumab + FOLFOX treatment arms, participants will be randomized in a 1:1 ratio to either MK-2010 + FOLFOX or Pembrolizumab + FOLFOX. For all other treatment arms, participants will be allocated to their respective treatment arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has radiographically measurable disease per protocol * If to receive oral study treatment, has the ability to swallow and retain oral medication and does not have gastrointestinal abnormalities that may alter absorption * Has well-controlled human immunodeficiency virus (HIV) on antiretroviral therapy (ART) if diagnosed with HIV * Has adequate organ function per protocol
Exclusion criteria
* Has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease if diagnosed with HIV * Has a history of posterior reversible encephalopathy syndrome (PRES) or seizure disorder * Has hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or more severe liver cirrhosis * Has a history of confirmed inflammatory bowel disease * Has a serious active nonhealing wound, ulcer, and/or bone fracture * Has a history of myocarditis or cardiomyopathy * Has a history of or current severe cardiovascular and cerebrovascular diseases * Is currently receiving any anticoagulants * Has a diagnosis of immunodeficiency * Has a known additional malignancy that is progressing or required active treatment within the past 3 years * Has known active central nervous system metastases and/or carcinomatous meningitis * Has active autoimmune disease that required systemic treatment in the past 2 years (hormonal supplementation \[eg, thyroxine, insulin, or physiologic corticosteroid\] is allowed) * Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD * Has a history of stem cell/solid organ transplant * Has not adequately recovered from major surgery or from central venous access device placement, or has ongoing surgical complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AEs) | Up to approximately 24 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 24 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Number of Participants Who Experience Dose-Limiting Toxicity (DLT) | Up to approximately 28 days | DLT is defined as any drug-related adverse event (AE) observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next dose. |
| Objective Response Rate (ORR) | Up to approximately 24 months | ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to approximately 48 months | For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by BICR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. |
| Area Under the Curve From Time 0 to Last (AUC0-last) of MK-2010 | Predose and at designated time points up to approximately 24 months | Blood samples will be collected to determine the AUC0-last of MK-2010. |
| Area Under the Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) of MK-2010 | Predose and at designated time points up to approximately 24 months | Blood samples will be collected to determine the AUC0-tau of MK-2010. |
| Trough Concentration (Ctrough) of MK-2010 | Predose and at designated time points up to approximately 24 months | Blood samples will be collected to determine Ctrough of MK-2010. |
| Maximum Concentration (Cmax) of MK-2010 | Predose and at designated time points up to approximately 24 months | Blood samples will be collected to determine Cmax of MK-2010. |
| Incidence of Antidrug Antibodies (ADAs) to MK-2010 | Predose and at designated time points up to approximately 24 months | Blood samples will be collected to determine ADAs of MK-2010. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed