A Clinical Trial of MK-2750 in Participants With Advanced Solid Tumors (MK-2750-002)

• MK-2750 (Biological): Administered as an intravenous (IV) infusion
• 5-HT3 serotonin receptor antagonist (Drug): Administered as a premedication per the approved product label
• NK-1 receptor antagonist (Drug): Administered as a premedication per the approved product label
• Corticosteroid (Drug): Administered as a premedication per the approved product label
• Steroid mouthwash (dexamethasone or equivalent) (Drug): Administered orally per the approved product label as a rescue medication

Primary outcomes

• 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 outcomes

• 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.

Sex: All, ages: 18 Years to any

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

• Medical Director, Study director, Merck Sharp & Dohme LLC

NIH grants: 2025