Advanced Solid Tumors, Malignant Neoplasm
Conditions
Brief summary
MK-2750 is a trial medicine designed to treat certain solid tumors. MK-2750 is a type of treatment called an antibody drug conjugate (ADC). ADCs attach to a protein on cancer cells and deliver medicine to destroy those cells. The goals of this trial are to learn: * About the safety of MK-2750 and if participants tolerate it. Tolerate means participants will receive trial treatment in the trial unless they need to stop it due to health problems. * How many participants have cancer respond (get smaller or go away) to MK-2750
Interventions
DRUGCorticosteroid
Administered as a premedication per the approved product label
Administered orally per the approved product label as a rescue medication
BIOLOGICALMK-2750
Administered as an intravenous (IV) infusion
DRUG5-HT3 serotonin receptor antagonist
Administered as a premedication per the approved product label
DRUGNK-1 receptor antagonist
Administered as a premedication per the approved product label
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has histologically or cytologically confirmed advanced or metastatic squamous or nonsquamous non-small cell lung cancer (NSCLC); advanced or metastatic NSCLC; or advanced, unresectable, or metastatic pancreatic ductal adenocarcinoma (PDAC) * Has histologically confirmed unresectable locally advanced or metastatic colorectal adenocarcinoma or squamous cell carcinoma of the esophagus; advanced or metastatic adenocarcinoma of the esophagus, gastroesophageal junction (GEJ), or gastric/stomach that is considered incurable by local therapies; or recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies * Has provided archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated * If human immunodeficiency virus (HIV)-infected, has well-controlled HIV on antiretroviral therapy (ART) * If hepatitis B surface antigen (HBsAg)-positive, has received HBV antiviral therapy for at least 4 weeks and has undetectable hepatitis B virus (HBV) viral load * If history of hepatitis C virus (HCV) infection, has undetectable HCV viral load * Has adequate organ function
Exclusion criteria
* Is HIV-infected with history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to allocation/randomization * Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids * 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 * Has a history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, except for a history of radiation pneumonitis that did not require steroids; current diagnosis of ILD; or clinical or radiographic suspicion of ILD for which the diagnosis of ILD cannot be ruled out * Has active infection requiring systemic therapy other than those permitted in the protocol * Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing * Has uncontrolled significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval by Fridericia (QTcF) to \>470 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention * Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention * Has not adequately recovered from major surgery or has ongoing surgical complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience an Adverse Event (AE) | Up to approximately 2 years | 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 Discontinued Study Intervention Due to an AE | Up to approximately 2 years | 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. |
| Objective Response Rate (ORR) | Up to approximately 2 years | 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 investigator will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to approximately 2 years | For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by investigator, 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. |
| Maximum Plasma Concentration (Cmax) of MK-2750 Free Payload | Predose and at designated time points up to approximately 2 years | Blood samples will be collected to determine Cmax of MK-2750 Free Payload. |
| Cmax of MK-2750 Total Antibodies (TAb) | Predose and at designated time points up to approximately 2 years | Blood samples will be collected to determine Cmax of MK-2750 Total Antibodies. |
| Cmax of MK-2750 Antibody-Drug Conjugate (ADC) | Predose and at designated time points up to approximately 2 years | Blood samples will be collected to determine Cmax of MK-2750 Antibody-Drug Conjugate. |
| Trough Concentration (Ctrough) of MK-2750 Free Payload | Predose and at designated time points up to approximately 2 years | Blood samples will be collected to determine Ctrough of MK-2750 Free Payload. |
| Ctrough of MK-2750 TAb | Predose and at designated time points up to approximately 2 years | Blood samples will be collected to determine Ctrough of MK-2750 Total Antibodies. |
| Ctrough of MK-2750 ADC | Predose and at designated time points up to approximately 2 years | Blood samples will be collected to determine Ctrough of MK-2750 Antibody-Drug Conjugate. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed