Advanced Solid Tumor, Cervical Cancer, Cutaneous Squamous Cell Carcinoma, Esophageal Squamous Cell Carcinoma, HepatoCellular Carcinoma, Merkel Cell Carcinoma, Mesothelioma, MSI-H/dMMR Tumors, Nasopharyngeal Carcinoma, PD-L1 Amplified Tumor (9p24.1), Small-cell Lung Cancer, Urothelial Carcinoma
Conditions
Keywords
Advanced Solid Tumor
Brief summary
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and early clinical activity of INCB099280 in participants with select solid tumors
Interventions
DRUGINCB099280
INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study consists of 2 parts. Part 1 is a dose-escalation design to identify the maximum tolerant dose and/or pharmacologically active dose for INCB099280. Part 2 is an expansion at 1 or more dose levels to further explore safety, preliminary efficacy, pharmacokinetic, and pharmacodynamic effects.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have disease progression after treatment with available therapies that are known to confer clinical benefit or must be intolerant to or ineligible for standard treatment. * Histologically confirmed advanced solid tumors (protocol-defined select solid tumors) with measurable lesions per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) that are considered nonamenable to surgery or other curative treatments or procedures. * Eastern Cooperative Oncology Group performance status score of 0 or 1. * Life expectancy \> 12 weeks. * Willingness to avoid pregnancy or fathering children.
Exclusion criteria
* Laboratory values outside the Protocol-defined ranges. * Clinically significant cardiac disease. * History or presence of an electrocardiogram that, in the investigator's opinion, is clinically meaningful. * Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases). * Known additional malignancy that is progressing or requires active treatment. * Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy (including prior IO) and/or complications from prior surgical intervention before starting study treatment. * Prior receipt of an anti-PD-L1 therapy. * Treatment with anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug. * A 28-day washout for systemic antibiotics is required. * Probiotic usage while on study and during screening is prohibited. * Active infection requiring systemic therapy. * Known history of Human Immunodeficiency Virus (HIV) * Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment-emergent adverse events | Up to approximately 25 months | Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 30 days after last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| tmax of INCB099280 | Up to approximately 3 months | Time to maximum plasma concentration |
| Cmin of INCB099280 | Up to approximately 3 months | Minimum observed plasma concentration over the dose interval |
| AUC0-t of INCB099280 | Up to approximately 3 months | Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t |
| Cmax of INCB099280 | Up to approximately 3 months | Maximum observed plasma concentration |
| λz of INCB099280 | Up to approximately 3 months | Terminal elimination rate constant |
| CL/F of INCB099280 | Up to approximately 3 months | Oral dose clearance |
| Vz/F of INCB099280 | Up to approximately 3 months | Apparent oral dose volume of distribution |
| t½ of INCB099280 | Up to approximately 3 months | Apparent terminal-phase disposition half-life |
Countries
Australia, Belgium, France, Japan, United States
Outcome results
None listed