A Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB086550 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, pharmacodynamics, and early clinical activity of INCB086550 in participants with advanced solid tumors who have failed prior treatments.

Official Title
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A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB086550 in Participants With Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: INCB086550


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed advanced solid tumors with measurable lesions per RECIST v1.1 or RANO for primary brain tumors that are considered nonamenable to surgery or other curative treatments or procedures. Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measurable per RECIST v1.1 if progression has been demonstrated in the lesion. Willingness to undergo a tumor biopsy to obtain tumor tissue,Pretreatment and on-treatment tumor biopsies are required. Must have disease progression after treatment with available therapies that are known to confer clinical benefit or who are intolerant to or ineligible for standard treatment. There is no limit to the number of prior treatment regimens. Eastern Cooperative Oncology Group performance status score of 0 or 1. Life expectancy > 12 weeks. Willingness to avoid pregnancy or fathering children. Part 2 Expansion Cohort 2-A only: Participants with any type of solid tumor that has a local regulatory approval for an anti-PD-1 therapy. Other tumor types may be enrolled with medical monitor approval. Participants must have had confirmed disease progression on a prior anti-PD-1 monoclonal antibody. Part 2 Expansion Cohort 2-B only: Participants with select solid tumors who are immunotherapy-naïve. Part 3 MSI-H or dMMR Expansion Cohort only (Enrolled ex-United States only): Participants with any MSI-H or dMMR solid tumor who are immunotherapy-naïve. Part 4 HPV-driven expansion cohort only: Participants with any HPV-positive solid tumor who have received prior standard therapy. Note: HPV-positive status determined by a local laboratory using p16 IHC, polymerase chain reaction methods, or other locally-available method to detect HPV Exclusion Criteria: Laboratory values not within the Protocol-defined range. 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. Participants who have previously treated and clinically stable brain or CNS metastases and have not required steroids for at least 7 days before study treatment are eligible. Known additional malignancy that is progressing or requires active treatment. Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment. Treatment with anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug. Active infection requiring systemic therapy. Active HBV or HCV infection that requires treatment. Known history of HIV (HIV 1/2 antibodies). Known hypersensitivity or severe reaction to any component of study drug or formulation components. Prior receipt of an anti-PD-L1 therapy for all participants. Presence of a gastrointestinal condition that may affect drug absorption.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INCB086550<br> | Drug: INCB086550<br>* INCB086550 will be orally administered once or twice daily in continuous or intermittent dose schedules.<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. | Baseline through 90 days after end of treatment, estimated up to 12 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of INCB086550 in fasted and food effect conditions | Maximum observed plasma or serum concentration. | Approximately 1 month | 
| tmax of INCB086550 in fasted and food effect conditions | Time to maximum concentration. | Approximately 1 month | 
| AUC0-tau of INCB086550 in fasted and food effect conditions | Area under the plasma or serum concentration-time curve from time = 0 to the end of dosing period at steady state | Approximately 1 month | 
| AUC 0-t and/or AUC0-∞ of INCB086550 in fasted and food effect conditions | Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration, or Area under the single-dose plasma concentration-time curve from Hour 0 to infinity | Approximately 1 month | 
| t½ of INCB086550 | Apparent terminal-phase disposition half-life. | Approximately 1 month | 
| λz of INCB086550 | Apparent terminal-phase disposition rate constant | Approximately 1 month | 
| CL/F of INCB086550 | Apparent oral dose clearance. | Approximately 1 month | 
| Vz/F of INCB086550 | Apparent oral dose volume of distribution. | Approximately 1 month | 
| Pharmacokinetic/pharmacodynamics correlation | Evaluation of the ability of INCB086550 to modulate PD-L1 expression levels as assessed by flow cytometry protein analyses. | Approximately 1 month | 
| Objective response rate | Defined as the percentage of participants having complete response (CR) or partial response (PR) by investigator assessment of radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or response assessment in Neuro-Oncology (RANO). | Every 8 weeks for the duration of study participation; estimated to be 12 months. | 
| Disease control rate | Defined as the percentage of participants having CR, PR, or stable disease ≥ 12 weeks by investigator assessment of radiographic disease assessments per RECIST v1.1 or response assessment in Neuro-Oncology (RANO). | Every 8 weeks for the duration of study participation; estimated to be 12 months. | 
| Duration of response | Defined as the time from the first documented evidence of CR or PR until the earliest date of disease progression by investigator assessment per RECIST v1.1 for response assessment in Neuro-Oncology (RANO), or death due to any cause, if occurring sooner than progression. | Every 8 weeks for the duration of study participation; estimated to be 12 months. | 
| Cmin of INCB086550 in fasted and food effect conditions | Minimum observed plasma or serum concentration of INCB086550 | Approximately 1 month | 

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