Clinical trial NCT04272034: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Select Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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)
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)
Keywords: Advanced solid tumors
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2020-02-17
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Number of treatment-emergent adverse events
timeFrame: Up to approximately 25 months
Secondary outcomes:
measure: Cmax of INCB099318
timeFrame: Up to approximately 3 months
measure: tmax of INCB099318
timeFrame: Up to approximately 3 months
measure: Cmin of INCB099318
timeFrame: Up to approximately 3 months
measure: AUC0-t of INCB099318
timeFrame: Up to approximately 3 months
measure: t½ of INCB099318
timeFrame: Up to approximately 3 months
measure: λz of INCB099318
timeFrame: Up to approximately 3 months
measure: CL/F of INCB099318
timeFrame: Up to approximately 3 months
measure: Vz/F of INCB099318
timeFrame: Up to approximately 3 months
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Greenville
country: United States
facility: Prisma Health Cancer Institute Faris
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (Uza)
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Leuven - Gasthuisberg
city: Copenhagen
country: Denmark
facility: Rigshospitalet Uni of Hospital of Copenhagen
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Helsinki
country: Finland
facility: Docrates Cancer Center
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Solna
country: Sweden
facility: Karolinska University Hospital Solna
city: Uppsala
country: Sweden
facility: Uppsala Universitet - Akademiska Sjukhuset
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: London
country: United Kingdom
facility: Guys and St Thomas Nhs Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden Hospital Nhs Trust London
city: London
country: United Kingdom
facility: Imperial College Healthcare Nhs Trust - Hammersmith Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust
Study officials:
affiliation: Incyte Corporation
name: Louis Viviers, MD
role: STUDY_DIRECTOR
References: