Clinical trial NCT05853367: Study of MK-0472 in Participants With Advanced/Metastatic Solid Tumors (MK-0472-001)
Official title: A Phase 1/1b Open-label, Multicenter Clinical Study of MK-0472 as Monotherapy and Combination Therapy in Participants With Advanced/Metastatic Solid Tumors.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Solid Tumors
Advanced Solid Tumors
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (SHP-2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2023-05-10
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
timeFrame: At the end of Cycle 1 (each cycle is 21 days)
measure: Number of Participants Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 56 months
measure: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
timeFrame: Up to approximately 56 months
Secondary outcomes:
measure: Area Under the Concentration Time-curve From Time 0 to the End of the Dosing Period (AUCtau) of MK-0472
timeFrame: At predetermined timepoints predose and postdose up to Cycle 6 (Each cycle length = 21 Days)
measure: Lowest Plasma Concentration (Ctrough) of MK-0472
timeFrame: At predetermined timepoints Predose up to Cycle 6 (Each cycle length = 21 Days)
measure: Maximum Plasma Concentration (Cmax) of MK-0472
timeFrame: At predetermined timepoints postdose up to Cycle 6 (Each cycle length = 21 Days)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital ( Site 0002)
state: Illinois
city: Louisville
country: United States
facility: The University of Louisville, James Graham Brown Cancer Center ( Site 0004)
state: Kentucky
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center ( Site 0001)
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 0005)
state: New Jersey
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0101)
state: Ontario
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal-Unit for Innovative Therapies ( Site 0100)
state: Quebec
city: Santiago.
country: Chile
facility: Bradfordhill ( Site 0702)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Centro de Estudios Clínicos SAGA ( Site 0701)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Fundacion Arturo Lopez Perez ( Site 0700)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Centro de Investigacion Clinicadela Universidad Catolica ( Site 0703)
state: Region M. De Santiago
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 0304)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 0303)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 0301)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 0300)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0302)
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 0401)
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne ( Site 0400)
state: Pomorskie
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia - L'Hospitalet-Medical Oncology ( Site 0501)
state: Cataluna
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron ( Site 0500)
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio ( Site 0503)
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG) ( Site 0202)
state: Geneve
city: St.Gallen
country: Switzerland
facility: Cantonal Hospital St.Gallen-Oncology & Hematology ( Site 0201)
state: Sankt Gallen
city: Bellinzona
country: Switzerland
facility: Ospedale Regionale Bellinzona e Valli ( Site 0200)
state: Ticino
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: