RecruitingInterventionalPhase 1

A Phase 1, Open-Label, Multicenter Study to Assess Safety, Tolerability, Pharmacokinetics, and Efficacy of MK-4716 as Monotherapy and as Part of Combination Therapy in Participants With KRAS-Altered Advanced or Metastatic Solid Tumors

NCT ID: NCT07247110Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-03

Summary

Researchers are looking for new ways to treat certain advanced or metastatic solid tumors. The goal of this study is to learn about the safety of MK-4716 and if people tolerate it when taken alone or with other treatments.

Arms & interventions

DrugMK-4716
Oral administration
BiologicalPembrolizumab
Intravenous administration
BiologicalCetuximab
Intravenous administration

Outcome measures

Primary

Number of Participants Who Experience One or More Dose-Limiting Toxicities (DLT)
A DLT is defined as the occurrence of protocol-specified toxicities, unless clearly related to disease progression or intercurrent illness.
Time frame: Up to approximately 28 days
Number of Participants Who Experience an Adverse Event (AE)
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.
Time frame: Up to approximately 4 years
Number of Participants Who Discontinue Study Intervention Due to an AE
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.
Time frame: Up to approximately 4 years

Secondary

Area Under the Concentration-Time Curve (AUC) of MK-4716
Time frame: At designated timepoints (up to approximately 58 days)
Maximum Plasma Concentration (Cmax) of MK-4716
Time frame: At designated timepoints (up to approximately 58 days)
Trough Plasma Concentration (Ctrough) of MK-4716
Time frame: At designated timepoints (up to approximately 19 months)
Half-Life (t1/2) of MK-4716
Time frame: At designated timepoints (up to approximately 58 days)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * Subset of arm MK-4716 Dose Escalation and subset of arm MK-4716 + Cetuximab: Has a confirmed diagnosis of locally advanced unresectable or metastatic solid tumor * Subset of arm MK-4716 Dose Escalation and subset of arm MK-4716 + Cetuximab: Must demonstrate presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) alteration * Subset of arm MK-4716 Dose Escalation and subset of arm MK-4716 + Cetuximab: Has received at least 1 prior line of systemic therapy for locally advanced unresectable or metastatic disease * Arm MK-4716 + Pembrolizumab: Has a confirmed diagnosis of metastatic non-small cell lung cancer * Arm MK-4716 + Pembrolizumab: Must demonstrate presence of KRAS alteration * Arm MK-4716 + Pembrolizumab: Must be untreated * Has measurable disease * Has the ability to swallow and retain oral medication Exclusion Criteria: * Arm MK-4716 + Pembrolizumab: Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention * Arm MK-4716 + Pembrolizumab: Has received any prior immunotherapy and was discontinued from that treatment * Arm MK-4716 + Pembrolizumab: Has active autoimmune disease that has required systemic treatment in the past 2 years. Hormonal supplementation (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed * History of human immunodeficiency virus infection * Has a known additional malignancy that is progressing or has required active treatment within the past 2 years * Has a known active central nervous system metastases and/or carcinomatous meningitis * History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Has active infection requiring systemic therapy * Has Hepatitis B or Hepatitis C virus infection * History of stem cell/solid organ transplant * Has not adequately recovered from major surgery or has ongoing surgical complications

Study locations (3)

Rutgers Cancer Institute of New Jersey ( Site 0052)

New Brunswick, New Jersey, 08903

Recruiting

Study Coordinator · Contact

732-253-3939

NEXT Oncology ( Site 0051)

Irving, Texas, 75039

Recruiting

Study Coordinator · Contact

972-893-8800

NEXT Virginia ( Site 0054)

Fairfax, Virginia, 22031

Recruiting

Study Coordinator · Contact

703-783-4510