Back to resultsSafety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Advanced Solid Tumors
Primary Purpose
Advanced Solid Tumors, MSI-H/dMMR Tumors, Cutaneous Squamous Cell Carcinoma
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
INCB099318
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Solid Tumors focused on measuring Advanced 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.
Sites / Locations
- Hackensack University Medical Center
- Prisma Health Cancer Institute Faris
- Vanderbilt-Ingram Cancer Center
- Universitair Ziekenhuis Brussel
- Institut Jules Bordet
- Universitair Ziekenhuis Antwerpen (Uza)
- Ghent University Hospital
- Universitaire Ziekenhuis Leuven - Gasthuisberg
- Rigshospitalet Uni of Hospital of Copenhagen
- Helsinki University Central Hospital
- Docrates Cancer Center
- Tampere University Hospital
- Turku University Hospital
- Haukeland University Hospital
- Oslo University Hospital
- Sahlgrenska University Hospital
- Karolinska University Hospital Solna
- Uppsala Universitet - Akademiska Sjukhuset
- Western General Hospital
- St James University Hospital
- Guys and St Thomas Nhs Foundation Trust
- The Royal Marsden Hospital Nhs Trust London
- Imperial College Healthcare Nhs Trust - Hammersmith Hospital
- Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Arm Description
Participants with select solid tumors who are immunotherapy treatment-naive
Participants with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors who are immunotherapy treatment-naïve.
Participants with progression of any solid tumor treated with an approved anti-PD-1 monoclonal antibody therapy
Outcomes
Primary Outcome Measures
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 up to 30 days after last dose of study drug.
Secondary Outcome Measures
Cmax of INCB099318
Maximum observed plasma concentration
tmax of INCB099318
Time to maximum plasma concentration
Cmin of INCB099318
Minimum observed plasma concentration over the dose interval
AUC0-t of INCB099318
Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t
t½ of INCB099318
Apparent terminal-phase disposition half-life
λz of INCB099318
Terminal elimination rate constant
CL/F of INCB099318
Oral dose clearance
Vz/F of INCB099318
Apparent oral dose volume of distribution
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04272034
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 26, 2021 (Actual)
Primary Completion Date
January 30, 2026 (Anticipated)
Study Completion Date
June 20, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of INCB099318 in select solid tumors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
105 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Participants with select solid tumors who are immunotherapy treatment-naive
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Participants with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors who are immunotherapy treatment-naïve.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Participants with progression of any solid tumor treated with an approved anti-PD-1 monoclonal antibody therapy
Intervention Type
Drug
Intervention Name(s)
INCB099318
Intervention Description
INCB099318 administered orally in 20 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle.
Primary Outcome Measure Information:
Title
Number of treatment-emergent adverse events
Description
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 30 days after last dose of study drug.
Time Frame
Up to approximately 25 months
Secondary Outcome Measure Information:
Title
Cmax of INCB099318
Description
Maximum observed plasma concentration
Time Frame
Up to approximately 3 months
Title
tmax of INCB099318
Description
Time to maximum plasma concentration
Time Frame
Up to approximately 3 months
Title
Cmin of INCB099318
Description
Minimum observed plasma concentration over the dose interval
Time Frame
Up to approximately 3 months
Title
AUC0-t of INCB099318
Description
Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t
Time Frame
Up to approximately 3 months
Title
t½ of INCB099318
Description
Apparent terminal-phase disposition half-life
Time Frame
Up to approximately 3 months
Title
λz of INCB099318
Description
Terminal elimination rate constant
Time Frame
Up to approximately 3 months
Title
CL/F of INCB099318
Description
Oral dose clearance
Time Frame
Up to approximately 3 months
Title
Vz/F of INCB099318
Description
Apparent oral dose volume of distribution
Time Frame
Up to approximately 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Louis Viviers, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Prisma Health Cancer Institute Faris
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Universitair Ziekenhuis Brussel
City
Brussels
ZIP/Postal Code
01090
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
B-1070
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen (Uza)
City
Edegem
ZIP/Postal Code
02650
Country
Belgium
Facility Name
Ghent University Hospital
City
Ghent
ZIP/Postal Code
09000
Country
Belgium
Facility Name
Universitaire Ziekenhuis Leuven - Gasthuisberg
City
Leuven
ZIP/Postal Code
03000
Country
Belgium
Facility Name
Rigshospitalet Uni of Hospital of Copenhagen
City
Copenhagen
ZIP/Postal Code
02100
Country
Denmark
Facility Name
Helsinki University Central Hospital
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Facility Name
Docrates Cancer Center
City
Helsinki
ZIP/Postal Code
00180
Country
Finland
Facility Name
Tampere University Hospital
City
Tampere
ZIP/Postal Code
33520
Country
Finland
Facility Name
Turku University Hospital
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Haukeland University Hospital
City
Bergen
ZIP/Postal Code
05051
Country
Norway
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
00450
Country
Norway
Facility Name
Sahlgrenska University Hospital
City
Goteborg
ZIP/Postal Code
41345
Country
Sweden
Facility Name
Karolinska University Hospital Solna
City
Solna
ZIP/Postal Code
17164
Country
Sweden
Facility Name
Uppsala Universitet - Akademiska Sjukhuset
City
Uppsala
ZIP/Postal Code
75185
Country
Sweden
Facility Name
Western General Hospital
City
Edinburgh
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
Facility Name
St James University Hospital
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Guys and St Thomas Nhs Foundation Trust
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
The Royal Marsden Hospital Nhs Trust London
City
London
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
Imperial College Healthcare Nhs Trust - Hammersmith Hospital
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
Facility Name
Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Access to patient level data is not available for this study
Learn more about this trial
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Advanced Solid Tumors
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