Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Advanced Solid Tumors

Phase 1

Terminated

• Conditions: MSI-H/dMMR Tumors; Cutaneous Squamous Cell Carcinoma; Advanced Solid Tumors; PD-L1 Amplified Tumor (9p24.1); Nasopharyngeal Carcinoma; Cervical Cancer; Esophageal Squamous Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Anal Carcinoma; DNA Polymerase Epsilon Mutated Tumors (P286R and V411L)
• Interventions: Drug: INCB099318

• Registration Number: NCT04272034
• Lead Sponsor: Incyte Corporation

Brief Summary

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of INCB099318 in select solid tumors.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-13
• Study First Submitted QC: 2020-02-13
• Study First Posted: 2020-02-17
• Study Start: 2021-03-26
• Primary Completion: 2024-08-16
• Study Completion: 2024-08-16
• Status Verified: 2025-10
• Last Update Submitted: 2025-10-15
• Last Update Posted: 2025-10-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 105

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.
• ECOG performance status score of 0 or 1.
• Life expectancy > 12 weeks.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria

Exclusion Criteria:

• Laboratory values outside the Protocol-defined ranges.
• Clinically significant cardiac disease.
• History or presence of an ECG 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 HIV
• Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2	INCB099318	Participants with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors who are immunotherapy treatment-naïve.
Cohort 1	INCB099318	Participants with select solid tumors who are immunotherapy treatment-naive
Cohort 3	INCB099318	Participants with progression of any solid tumor treated with an approved anti-PD-1 monoclonal antibody therapy

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Cmin of INCB099318	Up to approximately 3 months	Minimum observed plasma concentration over the dose interval
AUC0-t of INCB099318	Up to approximately 3 months	Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t
t½ of INCB099318	Up to approximately 3 months	Apparent terminal-phase disposition half-life
λz of INCB099318	Up to approximately 3 months	Terminal elimination rate constant
Cmax of INCB099318	Up to approximately 3 months	Maximum observed plasma concentration
tmax of INCB099318	Up to approximately 3 months	Time to maximum plasma concentration
CL/F of INCB099318	Up to approximately 3 months	Oral dose clearance
Vz/F of INCB099318	Up to approximately 3 months	Apparent oral dose volume of distribution

Trial Locations

Locations (24)

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Prisma Health Cancer Institute Faris; 🇺🇸 Greenville, South Carolina, United States

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Universitair Ziekenhuis Brussel; 🇧🇪 Brussels, Belgium

Institut Jules Bordet; 🇧🇪 Brussels, Belgium

Universitair Ziekenhuis Antwerpen (Uza); 🇧🇪 Edegem, Belgium

Ghent University Hospital; 🇧🇪 Ghent, Belgium

Universitaire Ziekenhuis Leuven - Gasthuisberg; 🇧🇪 Leuven, Belgium

Rigshospitalet Uni of Hospital of Copenhagen; 🇩🇰 Copenhagen, Denmark

Helsinki University Central Hospital; 🇫🇮 Helsinki, Finland

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