Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors

Sponsor

Incyte Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04242199

Collaborator

(none)

140

Enrollment

Locations

Arms

46.3

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and early clinical activity of INCB099280 in participants with select solid tumors

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor MSI-H/dMMR Tumors Cutaneous Squamous Cell Carcinoma Urothelial Carcinoma Cervical Cancer HepatoCellular Carcinoma Esophageal Squamous Cell Carcinoma Merkel Cell Carcinoma Small-cell Lung Cancer Mesothelioma PD-L1 Amplified Tumor (9p24.1) Nasopharyngeal Carcinoma	Drug: INCB099280	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The study consists of 2 parts. Part 1 is a dose-escalation design to identify the maximum tolerant dose and/or pharmacologically active dose for INCB099280. Part 2 is an expansion at 1 or more dose levels to further explore safety, preliminary efficacy, pharmacokinetic, and pharmacodynamic effects.The study consists of 2 parts. Part 1 is a dose-escalation design to identify the maximum tolerant dose and/or pharmacologically active dose for INCB099280. Part 2 is an expansion at 1 or more dose levels to further explore safety, preliminary efficacy, pharmacokinetic, and pharmacodynamic effects.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study Exploring the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Select Advanced Solid Tumors

Actual Study Start Date :

Aug 20, 2020

Anticipated Primary Completion Date :

May 31, 2024

Anticipated Study Completion Date :

Jun 28, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Participants with select solid tumors who are immunotherapy treatment-naive	Drug: INCB099280 INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle
Experimental: Cohort 2 Participants with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors who are immunotherapy treatment-naïve.	Drug: INCB099280 INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle
Experimental: Cohort 3 Participants with progression of any solid tumor treated with an approved anti-PD-1 monoclonal antibody therapy	Drug: INCB099280 INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle

Arm

Intervention/Treatment

Experimental: Cohort 1

Participants with select solid tumors who are immunotherapy treatment-naive

Drug: INCB099280

INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle

Experimental: Cohort 2

Participants with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors who are immunotherapy treatment-naïve.

Drug: INCB099280

INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle

Experimental: Cohort 3

Participants with progression of any solid tumor treated with an approved anti-PD-1 monoclonal antibody therapy

Drug: INCB099280

INCB099280 administered orally in 25 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle

Outcome Measures

Primary Outcome Measures

Number of treatment-emergent adverse events [Up to approximately 25 months]
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 INCB099280 [Up to approximately 3 months]
Maximum observed plasma concentration
tmax of INCB099280 [Up to approximately 3 months]
Time to maximum plasma concentration
Cmin of INCB099280 [Up to approximately 3 months]
Minimum observed plasma concentration over the dose interval
AUC0-t of INCB099280 [Up to approximately 3 months]
Area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t
t½ of INCB099280 [Up to approximately 3 months]
Apparent terminal-phase disposition half-life
λz of INCB099280 [Up to approximately 3 months]
Terminal elimination rate constant
CL/F of INCB099280 [Up to approximately 3 months]
Oral dose clearance
Vz/F of INCB099280 [Up to approximately 3 months]
Apparent oral dose volume of distribution

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
Eastern Cooperative Oncology Group performance status score of 0 or 1.
Life expectancy > 12 weeks.
Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

Laboratory values outside the Protocol-defined ranges.
Clinically significant cardiac disease.
History or presence of an electrocardiogram 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 Human Immunodeficiency Virus (HIV)
Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
2	Henry Ford Hospital	Detroit	Michigan	United States	48202
3	Upmc Cancercenter	Pittsburgh	Pennsylvania	United States	15232
4	Md Anderson Cancer Center	Houston	Texas	United States	77030
5	University of Washington	Seattle	Washington	United States	98195
6	Chris Obrien Lifehouse	Camperdown	New South Wales	Australia	02050
7	Austin Hospital	Heidelberg	Victoria	Australia	03084
8	Nucleus Network Pty Ltd	Melbourne	Victoria	Australia	03004
9	Linear Clinical Research	Nedlands	Western Australia	Australia	06009
10	Cliniques Universitaires Ucl Saint-Luc	Brussels		Belgium	01200
11	Institut Jules Bordet Clinical Trials Conduct Unit	Brussels		Belgium	B-1070
12	Universitair Ziekenhuis Antwerpen (Uza)	Edegem		Belgium	02650
13	Ghent University Hospital	Ghent		Belgium	09000
14	Universitaire Ziekenhuis Leuven - Gasthuisberg	Leuven		Belgium	03000
15	Complex Onclogy Center Plovdiv Eood	Plovdiv		Bulgaria	04004
16	Shatod Dr Marko Marko - Varna Ltd	Varna		Bulgaria
17	Institut de Cancerologie de L Ouest - Site Paul Papin	Angers		France	49000
18	Institut Bergonie	Bordeaux		France	33000
19	Chu Hopital de La Timone	Marseille Cedex 5		France	13385
20	Centre Eugene Marquis	Rennes		France	35042
21	Multifield Clinical Hospital No 4	Dnipro		Ukraine	49102
22	Ci of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection	Kharkiv		Ukraine	61166
23	Kherson Regional Oncologic Dispensary	Kherson		Ukraine	73000
24	Mi Kryviy Rih Center of Dnipropetrovsk Regional Council	Kryvyi Rih		Ukraine	50048
25	Volyn Regional Oncological Dispensary	Lutsk		Ukraine	43018
26	Rmi Sumy Regional Clinical Oncology Dispensary	Sumy		Ukraine	40022
27	Cne Ccch of Uzh Cc Oncological Center	Uzhgorod		Ukraine	88000
28	Medical Clinic Innovacia Llc	Vyshhorod		Ukraine	07352