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

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

Official Title
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A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Select Advanced Solid Tumors

Conditions
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Nasopharyngeal Carcinoma, Cyclin-dependent Kinase 12 Mutated Tumors, Basal Cell Carcinoma (Unresectable or Metastatic), Sarcomatoid Renal Cell Carcinoma, Clear Cell Ovarian or Endometrial Carcinoma, Anal Carcinoma, Squamous Cell Penile Carcinoma, DNA Polymerase Epsilon Mutated Tumors (P286R and V411L), Advanced Solid Tumors, MSI-H/dMMR Tumors, Cutaneous Squamous Cell Carcinoma, Urothelial Carcinoma, HCC, Cervical Cancer, Esophageal Squamous Cell Carcinoma, Merkel Cell Carcinoma, Small-cell Lung Cancer, Mesothelioma, PD-L1 Amplified Tumor (9p24.1)

Intervention / Treatment
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* Drug: INCB099318


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study consists of 2 parts. Part 1 is a dose-escalation design to identify the maximum tolerated dose and/or pharmacologically active dose for INCB099318. Part 2 is an expansion at 1 or more dose levels to further explore safety, preliminary efficacy, pharmacoketics, and pharmacodynamic effects.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants with select solid tumors who are immunotherapy treatment-naive | Drug: INCB099318<br>* INCB099318 administered orally in 20 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle.<br>|
| Experimental: Cohort 2<br>Participants with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors who are immunotherapy treatment-naïve. | Drug: INCB099318<br>* INCB099318 administered orally in 20 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle.<br>|
| Experimental: Cohort 3<br>Participants with progression of any solid tumor treated with an approved anti-PD-1 monoclonal antibody therapy | Drug: INCB099318<br>* INCB099318 administered orally in 20 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle.<br>|

What is the study measuring?
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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 INCB099318 | Maximum observed plasma concentration | Up to approximately 3 months | 
| tmax of INCB099318 | Time to maximum plasma concentration | Up to approximately 3 months | 
| Cmin of INCB099318 | Minimum observed plasma concentration over the dose interval | Up to approximately 3 months | 
| AUC0-t of INCB099318 | 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 INCB099318 | Apparent terminal-phase disposition half-life | Up to approximately 3 months | 
| λz of INCB099318 | Terminal elimination rate constant | Up to approximately 3 months | 
| CL/F of INCB099318 | Oral dose clearance | Up to approximately 3 months | 
| Vz/F of INCB099318 | Apparent oral dose volume of distribution | Up to approximately 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumors