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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03762447
• Other study ID #: INCB 86550-102
• Status: Completed
• Phase: Phase 1
• Start date: December 10, 2018
• Est. completion date: November 17, 2023

Study information

• Verified date: November 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: November 17, 2023
• Est. primary completion date: November 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• INCB086550
INCB086550 will be orally administered once or twice daily in continuous or intermittent dose schedules.

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen (Uza)	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuis Leuven - Gasthuisberg	Leuven
France	Chu Hopital de La Timone	Marseille Cedex 5
France	Icm Montpellier	Montpellier Cedex 5
France	Institut Curie	Paris
France	Institut Universitaire Du Cancer de Toulouse Oncopole	Toulouse
Italy	European Institute of Oncology	Milan
Italy	Fondazione Irccs Istituto Nazionale Dei Tumori	Milan
Italy	Istituto Nazionale Tumori Irccs Fondazione Pascale	Napoli
Italy	Irrcs Instituto Clinico Humanitas	Rozzano
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte	Siena
United Kingdom	Addenbrooke'S Hospital	Cambridge
United Kingdom	Guys and St Thomas Nhs Foundation Trust	London
United Kingdom	Imperial College Healthcare Nhs Trust - Hammersmith Hospital	London
United Kingdom	The Christie Nhs Foundation Trust Uk	Manchester
United Kingdom	Weston Park Hospital	Sheffield
United States	Aamc Oncology and Hematology	Annapolis	Maryland
United States	Md Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Jefferson University Hospitals	Philadelphia	Pennsylvania
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	H. Lee Moffitt Cancer Center and Research Institute Hospital	Tampa	Florida
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cmax of INCB086550 in fasted and food effect conditions	Maximum observed plasma or serum concentration.	Approximately 1 month
Secondary	tmax of INCB086550 in fasted and food effect conditions	Time to maximum concentration.	Approximately 1 month
Secondary	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
Secondary	AUC 0-t and/or AUC0-8 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
Secondary	t½ of INCB086550	Apparent terminal-phase disposition half-life.	Approximately 1 month
Secondary	?z of INCB086550	Apparent terminal-phase disposition rate constant	Approximately 1 month
Secondary	CL/F of INCB086550	Apparent oral dose clearance.	Approximately 1 month
Secondary	Vz/F of INCB086550	Apparent oral dose volume of distribution.	Approximately 1 month
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Cmin of INCB086550 in fasted and food effect conditions	Minimum observed plasma or serum concentration of INCB086550	Approximately 1 month