Clinical trial NCT03762447: A Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB086550 in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB086550 in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: solid tumors
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-12-03
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of treatment-emergent adverse events
timeFrame: Baseline through 90 days after end of treatment, estimated up to 12 months.
Secondary outcomes:
measure: Cmax of INCB086550 in fasted and food effect conditions
timeFrame: Approximately 1 month
measure: tmax of INCB086550 in fasted and food effect conditions
timeFrame: Approximately 1 month
measure: AUC0-tau of INCB086550 in fasted and food effect conditions
timeFrame: Approximately 1 month
measure: AUC 0-t and/or AUC0-∞ of INCB086550 in fasted and food effect conditions
timeFrame: Approximately 1 month
measure: t½ of INCB086550
timeFrame: Approximately 1 month
measure: λz of INCB086550
timeFrame: Approximately 1 month
measure: CL/F of INCB086550
timeFrame: Approximately 1 month
measure: Vz/F of INCB086550
timeFrame: Approximately 1 month
measure: Pharmacokinetic/pharmacodynamics correlation
timeFrame: Approximately 1 month
measure: Objective response rate
timeFrame: Every 8 weeks for the duration of study participation; estimated to be 12 months.
measure: Disease control rate
timeFrame: Every 8 weeks for the duration of study participation; estimated to be 12 months.
measure: Duration of response
timeFrame: Every 8 weeks for the duration of study participation; estimated to be 12 months.
measure: Cmin of INCB086550 in fasted and food effect conditions
timeFrame: Approximately 1 month
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute Hospital
state: Florida
city: Annapolis
country: United States
facility: Aamc Oncology and Hematology
state: Maryland
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson University Hospitals
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (Uza)
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Leuven - Gasthuisberg
city: Marseille Cedex 5
country: France
facility: Chu Hopital de La Timone
city: Montpellier Cedex 5
country: France
facility: Icm Montpellier
city: Paris
country: France
facility: Institut Curie
city: Toulouse
country: France
facility: Institut Universitaire Du Cancer de Toulouse Oncopole
city: Milan
country: Italy
facility: Fondazione Irccs Istituto Nazionale Dei Tumori
city: Milan
country: Italy
facility: European Institute of Oncology
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione Pascale
city: Rozzano
country: Italy
facility: Irrcs Instituto Clinico Humanitas
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte
city: Cambridge
country: United Kingdom
facility: Addenbrooke'S Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas Nhs Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare Nhs Trust - Hammersmith Hospital
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust Uk
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
Study officials:
affiliation: Incyte Corporation
name: Kevin O'Hayer, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.