Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors

A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Select Advanced Solid Tumors

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

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Nasopharyngeal Carcinoma; Mesothelioma; Advanced Solid Tumor; Small-cell Lung Cancer; Esophageal Squamous Cell Carcinoma; Urothelial Carcinoma; Merkel Cell Carcinoma; HepatoCellular Carcinoma; Cutaneous Squamous Cell Carcinoma; MSI-H/dMMR Tumors; PD-L1 Amplified Tumor (9p24.1)
• Intervention / Treatment: Drug: INCB099280

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 02050
      • Chris OBrien Lifehouse
  • Victoria
    • Heidelberg, Victoria, Australia, 03084
      • Austin Hospital
    • Melbourne, Victoria, Australia, 03004
      • Nucleus Network Pty Ltd
  • Western Australia
    • Nedlands, Western Australia, Australia, 06009
      • Linear Clinical Research
• Belgium
  • Brussels, Belgium, 01200
    • Cliniques Universitaires Ucl Saint-Luc
  • Brussels, Belgium, B-1070
    • Institut Jules Bordet Clinical Trials Conduct Unit
  • Edegem, Belgium, 02650
    • Universitair Ziekenhuis Antwerpen (Uza)
  • Ghent, Belgium, 09000
    • Ghent University Hospital
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
• France
  • Angers, France, 49000
    • Institut de Cancerologie de L Ouest - Site Paul Papin
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Marseille Cedex 5, France, 13385
    • CHU Hôpital de la Timone
  • Rennes, France, 35042
    • Centre Eugène Marquis
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Japan
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Upmc Cancercenter
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants with select solid tumors who are immunotherapy treatment-naive	Drug: INCB099280; INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle
Experimental: Cohort 2; Participants with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors who are immunotherapy treatment-naïve.	Drug: INCB099280; INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle
Experimental: Cohort 3; Participants with progression of any solid tumor treated with an approved anti-PD-1 monoclonal antibody therapy	Drug: INCB099280; INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment-emergent adverse events	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.	Up to approximately 25 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of INCB099280	Maximum observed plasma concentration	Up to approximately 3 months
tmax of INCB099280	Time to maximum plasma concentration	Up to approximately 3 months
Cmin of INCB099280	Minimum observed plasma concentration over the dose interval	Up to approximately 3 months
AUC0-t of INCB099280	Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t	Up to approximately 3 months
t½ of INCB099280	Apparent terminal-phase disposition half-life	Up to approximately 3 months
λz of INCB099280	Terminal elimination rate constant	Up to approximately 3 months
CL/F of INCB099280	Oral dose clearance	Up to approximately 3 months
Vz/F of INCB099280	Apparent oral dose volume of distribution	Up to approximately 3 months

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Incyte Medical Monitor, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2020
• Primary Completion (Actual): August 29, 2024
• Study Completion (Actual): November 21, 2024

Study Registration Dates

• First Submitted: January 23, 2020
• First Submitted That Met QC Criteria: January 23, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): July 14, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Advanced Solid Tumor
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Infections; Virus Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; DNA Virus Infections; Esophageal Diseases; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Neoplasms, Squamous Cell; Otorhinolaryngologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Tumor Virus Infections; Polyomavirus Infections; Esophageal Neoplasms; Carcinoma, Neuroendocrine; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Esophageal Squamous Cell Carcinoma; Neoplasms; Carcinoma; Mesothelioma; Carcinoma, Squamous Cell; Small Cell Lung Carcinoma; Carcinoma, Merkel Cell
• Other Study ID Numbers: INCB 99280-112; 2019-004967-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No