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

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: INCB086550

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 01000
    • Institut Jules Bordet
  • Edegem, Belgium, 02650
    • Universitair Ziekenhuis Antwerpen (UZA)
  • Gent, Belgium, 09000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
• France
  • Marseille Cedex 5, France, 13385
    • CHU Hôpital de la Timone
  • Montpellier Cedex 5, France, 34298
    • Icm Montpellier
  • Paris, France, 75005
    • Institut Curie
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer de Toulouse Oncopole
• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, 20141
    • European Institute of Oncology
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Rozzano, Italy, 20089
    • Irrcs Instituto Clinico Humanitas
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust - Hammersmith Hospital
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie Nhs Foundation Trust Uk
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute Hospital
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Aamc Oncology and Hematology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson University Hospitals
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INCB086550	Drug: INCB086550; INCB086550 will be orally administered once or twice daily in continuous or intermittent dose schedules.

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.	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

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Kevin O'Hayer, MD, PhD, Incyte Corporation

Publications and helpful links

General Publications

• Koblish HK, Wu L, Wang LS, Liu PCC, Wynn R, Rios-Doria J, Spitz S, Liu H, Volgina A, Zolotarjova N, Kapilashrami K, Behshad E, Covington M, Yang YO, Li J, Diamond S, Soloviev M, O'Hayer K, Rubin S, Kanellopoulou C, Yang G, Rupar M, DiMatteo D, Lin L, Stevens C, Zhang Y, Thekkat P, Geschwindt R, Marando C, Yeleswaram S, Jackson J, Scherle P, Huber R, Yao W, Hollis G. Characterization of INCB086550: A Potent and Novel Small-Molecule PD-L1 Inhibitor. Cancer Discov. 2022 Jun 2;12(6):1482-1499. doi: 10.1158/2159-8290.CD-21-1156.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2018
• Primary Completion (Actual): November 17, 2023
• Study Completion (Actual): November 17, 2023

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 30, 2018
• First Posted (Actual): December 3, 2018

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: solid tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: INCB 86550-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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