Study of MK-0472 in Participants With Advanced/Metastatic Solid Tumors (MK-0472-001)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumors; Metastatic Solid Tumors

Treatments: Biological: Pembrolizumab; Drug: MK-0472; Drug: MK-1084

Study type: Interventional

Funder types: Industry

Identifiers

NCT05853367

U1111-1310-1179 (Registry Identifier)

2024-516006-32-00 (Registry Identifier)

MK-0472-001 (Other Identifier)

0472-001

Details and patient eligibility

About

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.

Enrollment: 178 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 exclusion criteria include but are not limited to the following:

• Has not recovered to common terminology criteria for adverse events (CTCAE) Grade 1 or better from any adverse events that were due to cancer therapeutics administered more than 4 weeks earlier. Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study
• Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• History of hyperparathyroidism or hypercalcemia
• Has one or more of the following ophthalmological findings/conditions: a) Intraocular pressure >21 mm Hg and/or any diagnosis of glaucoma b) Diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion and c) Diagnosis of retinal degenerative disease
• Has clinically significant cardiovascular disease
• Bullous exfoliative skin disorders of any grade
• Known hypersensitivity to MK-0472, MK-1084, or pembrolizumab, or any of their excipients
• Received therapy with a proton-pump inhibitor or an H2 histamine blocker receptor antagonist within 7 days before the first scheduled day of study dosing
• Has discontinued prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor due to an adverse event
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before first dose
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
• 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. Participants with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention
• Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy
• Has history of pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has active infection requiring systemic therapy
• Has history of allogeneic tissue/solid organ transplant
• Have not adequately recovered from major surgery or have ongoing surgical complications

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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178 participants in 3 patient groups

MK-0472

Experimental group

Description:

Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens until disease progression or withdrawal/discontinuation.

Treatment:

Drug: MK-0472

MK-0472 + Pembrolizumab

Experimental group

Description:

Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens until disease progression or withdrawal/discontinuation, plus pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).

Treatment:

Drug: MK-0472

Biological: Pembrolizumab

MK-0472 + MK-1084

Experimental group

Description:

Participants receive MK-0472 via oral capsule according to one of the protocol-specified dosing regimens, plus MK-1084 via oral capsule until disease progression or withdrawal/discontinuation.

Treatment:

Drug: MK-1084

Drug: MK-0472