Study of Vimseltinib (DCC-3014) in Patients With Advanced Tumors and Tenosynovial Giant Cell Tumor

Inclusion criteria

Dose Escalation Phase:

• Patients ≥18 years of age
• Patients must have:

• advanced malignant solid tumors; or
• symptomatic TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening)
• Malignant solid tumor patients only: Able to provide a tumor tissue sample
• Must have 1 measurable lesion according to RECIST Version 1.1
• Malignant solid tumor patients only: Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate organ and bone marrow function
• If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
• Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.

Expansion Phase (Cohorts A and B)

• Patients ≥18 years of age
• Patients must have symptomatic TGCT for which surgical resection is not an option (tumor biopsy to confirm diagnosis required if no histology/pathology available at screening)

a) Expansion Cohort B: patients must have prior systemic treatment with anti-CSF1 or anti-CSF1R therapy, with the exception of imatinib or nilotinib

• Adequate organ and bone marrow function
• Must have at least 1 measurable lesion according to RECIST Version 1.1
• If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
• Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.

Exclusion criteria

Dose Escalation Phase:

• Received anticancer therapy or therapy for TGCT, including investigational therapy, within 2 weeks or 28 days for therapies with half-life (t1/2) longer than 3 days prior to the administration of study drug.
• Unresolved toxicity (Grade >1 or baseline) from previous anticancer therapy or TGCT therapy, excluding alopecia.
• Known active central nervous system (CNS) metastases.
• History or presence of clinically relevant cardiovascular abnormalities.
• Systemic arterial or venous thrombotic or embolic events.
• QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of long QT syndrome.
• Left ventricular ejection fraction (LVEF) <50%.
• Concurrent treatment with proton-pump inhibitor(s).
• Major surgery within 2 weeks of the first dose of study drug.
• Malabsorption syndrome or other illness that could affect oral absorption.
• Known human immunodeficiency virus, active hepatitis B, active hepatitis C, or active mycobacterium tuberculosis infection.
• If female, the patient is pregnant or lactating.
• Known allergy or hypersensitivity to any component of the study drug.
• Any other clinically significant comorbidities.

Expansion Phase (Cohorts A and B)

• Expansion Cohort A: received systemic therapy targeting CSF1 or CSF1R; previous therapy with imatinib and nilotinib is allowed.
• Expansion Cohort B: discontinued systemic therapy targeting anti-CSF1 or anti-CSF1R due to drug-induced liver injury.
• Treatment with therapy for TGCT, including investigational therapy, within 2 weeks or 28 days for therapies with a t1/2 longer than 3 days prior to the administration of the study drug.
• Known metastatic TGCT or other active cancer that requires concurrent treatment.
• QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of long QT syndrome.
• Left ventricular ejection fraction (LVEF) <55%.
• Concurrent treatment with proton-pump inhibitor(s).
• Major surgery within 2 weeks of the first dose of study drug.
• Any clinically significant comorbidities
• Malabsorption syndrome or other illness that could affect oral absorption.
• Known human immunodeficiency virus (HIV), active or chronic hepatitis B, active or chronic hepatitis C, or active mycobacterium tuberculosis infection.
• If female, the patient is pregnant or lactating.
• Known allergy or hypersensitivity to any component of the study drug.
• Contraindication for MRI
• Active liver or biliary disease, including evidence of fatty liver, nonalcoholic steatohepatitis (NASH), or cirrhosis