A Study to Evaluate the Safety, Tolerability, and Antitumor Activity of INCB001158 Plus Epacadostat, With or Without Pembrolizumab, in Advanced Solid Tumors

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03361228
• Collaborator: (none)
• Enrollment: 5
• Locations: 2
• Arms: 2
• Actual Duration (Months): 12.9
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and antitumor activity of INCB001158 plus epacadostat, with or without pembrolizumab, in participants with advanced or metastatic solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: INCB001158; Drug: Epacadostat; Drug: Pembrolizumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter, Nonrandomized, Dose-Escalation, and Tumor-Expansion Phase 1/2 Study to Evaluate the Safety, Tolerability, and Antitumor Activity of INCB001158 Plus Epacadostat (INCB024360), With or Without Pembrolizumab, in Subjects With Advanced Solid Tumors
• Actual Study Start Date: Mar 1, 2018
• Actual Primary Completion Date: Mar 30, 2019
• Actual Study Completion Date: Mar 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INCB001158 + Epacadostat + Pembrolizumab	Drug: INCB001158; Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.; Drug: Epacadostat; Epacadostat at the protocol-defined dose administered orally twice daily.; Other Names: INCB024360 ; Drug: Pembrolizumab; Pembrolizumab at the protocol-defined dose administered intravenously every 3 weeks.; Other Names: MK-3475
Experimental: INCB001158 + Epacadostat	Drug: INCB001158; Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.; Drug: Epacadostat; Epacadostat at the protocol-defined dose administered orally twice daily.; Other Names: INCB024360

Outcome Measures

Primary Outcome Measures

1. Phase 1 Only: Safety and Tolerability of INCB001158 in Combination With Epacadostat ± Pembrolizumab as Assessed by Number of Participants With a Treatment-emergent Adverse Event (TEAE) [Up to approximately 12 months per subject]

   TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment.

2. Phase 2 Only: Objective Response Rate (ORR) of INCB001158 in Combination With Epacadostat ± Pembrolizumab [Up to approximately 12 months per subject]

   Defined as percentage of subjects having a complete response (CR) or partial response (PR) based on investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

Secondary Outcome Measures

1. Phase 2 Only: Safety and Tolerability of INCB001158 in Combination With Epacadostat ± Pembrolizumab as Assessed by Number of Participants With a TEAE [Up to approximately 12 months per subject]

   TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment.

2. Phase 1 Only: ORR With INCB001158 in Combination With Epacadostat ± Pembrolizumab [Up to approximately 12 months per subject]

   Defined as percentage of subjects having a CR or PR based on investigator assessment per RECIST v1.1.

3. Disease Control Rate With INCB001158 in Combination With Epacadostat ± Pembrolizumab [Up to approximately 12 months per subject]

   Defined as percentage of subjects having CR, PR, or stable disease for at least 56 days based on investigator assessment per RECIST v1.1.

4. Duration of Response With INCB001158 in Combination With Epacadostat ± Pembrolizumab [Up to approximately 12 months per subject]

   Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression.

5. Progression-free Survival With INCB001158 in Combination With Epacadostat ± Pembrolizumab [Up to approximately 12 months per subject]

   Defined as the time from date of first dose of study treatment until the earliest date of disease progression (based on investigator assessment of per RECIST v1.1) or death due to any cause, if occurring sooner than progression.

6. Plasma Pharmacokinetic Profile of INCB001158 and Epacadostat [Up to approximately 1 month]

   Noncompartmental method of analysis will be used to analyze the plasma concentrations of INCB001158 and epacadostat.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• For Phase 1, subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (disease progression; subject intolerance is also allowable).

• For Phase 2, subjects with the following tumor types who meet protocol-defined criteria: advanced or metastatic NSCLC, melanoma, urothelial carcinoma, SCCHN, SCLC, and CRC.

• Presence of at least 1 measurable lesion by computed tomography or magnetic resonance imaging per RECIST v1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

• Resolution of all toxicities and any toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). Subjects with ≤ Grade 2 neuropathy are an exception and may enroll.

• Adequate renal, hepatic, and hematologic functions per protocol-defined laboratory parameters within ≤ 7 days before treatment initiation.

Exclusion Criteria:

• Participation in any other study in which receipt of an investigational study drug or device occurred within 2 weeks or 5 half-lives (whichever is longer) before first dose.

• Has received a prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before administration of study drug.

• Prior chemotherapy or targeted small molecule therapy within 2 weeks before administration of study treatment.

• Prior therapy with an IDO1 or arginase 1 inhibitor.

• Active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

• Receipt of a live vaccine within 30 days before the first dose of study treatment.

• Any history of serotonin syndrome after receiving serotonergic drugs.

• Use of protocol-defined prior/concomitant therapy.

• Known or suspected defect in the function of the urea cycle.

• History of gastrointestinal condition that may affect drug absorption.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294-3300
2	The University of Chicago Medicine	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• Incyte Corporation

Investigators

• Study Director: Sven Gogov, MD, Incyte Corporation

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 1, 2018

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT03361228
• Other Study ID Numbers: INCB 01158-202
• First Posted: Dec 4, 2017
• Last Update Posted: May 21, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Incyte Corporation: Non-small cell lung cancer (NSCLC); melanoma; urothelial carcinoma; squamous cell carcinoma of the head and neck (SCCHN); small cell lung cancer (SCLC); colorectal cancer (CRC); arginase 1 inhibitor; indoleamine 2,3-dioxygenase 1 inhibitor; programmed death-1 receptor (PD-1) inhibitor
• Additional relevant MeSH terms: Neoplasms; Pembrolizumab

Study Results

Participant Flow

Recruitment Details	The study was conducted at 3 different sites in US. A total of 10 patients were screened and 5 patients enrolled in study.
Pre-assignment Detail	No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
Period Title: Overall Study
STARTED	4	1
COMPLETED	0	0
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab	Total
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)	Total of all reporting groups
Overall Participants	0	0	0
Age () []
Sex: Female, Male (participants) []
Female
Male
Race/Ethnicity, Customized (participants) []
Race/Ethnicity, Customized (participants) []

Outcome Measures

1. Primary Outcome

Title	Phase 1 Only: Safety and Tolerability of INCB001158 in Combination With Epacadostat ± Pembrolizumab as Assessed by Number of Participants With a Treatment-emergent Adverse Event (TEAE)
Description	TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment.
Time Frame	Up to approximately 12 months per subject

Outcome Measure Data

Analysis Population Description

No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
Measure Participants	0	0

2. Primary Outcome

Title	Phase 2 Only: Objective Response Rate (ORR) of INCB001158 in Combination With Epacadostat ± Pembrolizumab
Description	Defined as percentage of subjects having a complete response (CR) or partial response (PR) based on investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Time Frame	Up to approximately 12 months per subject

Outcome Measure Data

Analysis Population Description

Data was not collected as no participants were enrolled in Phase 2 of the study

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
Measure Participants	0	0

3. Secondary Outcome

Title	Phase 2 Only: Safety and Tolerability of INCB001158 in Combination With Epacadostat ± Pembrolizumab as Assessed by Number of Participants With a TEAE
Description	TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment.
Time Frame	Up to approximately 12 months per subject

Outcome Measure Data

Analysis Population Description

Data was not collected as no participants were enrolled in Phase 2 of the study

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
Measure Participants	0	0

4. Secondary Outcome

Title	Phase 1 Only: ORR With INCB001158 in Combination With Epacadostat ± Pembrolizumab
Description	Defined as percentage of subjects having a CR or PR based on investigator assessment per RECIST v1.1.
Time Frame	Up to approximately 12 months per subject

Outcome Measure Data

Analysis Population Description

No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
Measure Participants	0	0

5. Secondary Outcome

Title	Disease Control Rate With INCB001158 in Combination With Epacadostat ± Pembrolizumab
Description	Defined as percentage of subjects having CR, PR, or stable disease for at least 56 days based on investigator assessment per RECIST v1.1.
Time Frame	Up to approximately 12 months per subject

Outcome Measure Data

Analysis Population Description

No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
Measure Participants	0	0

6. Secondary Outcome

Title	Duration of Response With INCB001158 in Combination With Epacadostat ± Pembrolizumab
Description	Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression.
Time Frame	Up to approximately 12 months per subject

Outcome Measure Data

Analysis Population Description

No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
Measure Participants	0	0

7. Secondary Outcome

Title	Progression-free Survival With INCB001158 in Combination With Epacadostat ± Pembrolizumab
Description	Defined as the time from date of first dose of study treatment until the earliest date of disease progression (based on investigator assessment of per RECIST v1.1) or death due to any cause, if occurring sooner than progression.
Time Frame	Up to approximately 12 months per subject

Outcome Measure Data

Analysis Population Description

No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
Measure Participants	0	0

8. Secondary Outcome

Title	Plasma Pharmacokinetic Profile of INCB001158 and Epacadostat
Description	Noncompartmental method of analysis will be used to analyze the plasma concentrations of INCB001158 and epacadostat.
Time Frame	Up to approximately 1 month

Outcome Measure Data

Analysis Population Description

No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2

Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab	INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)	INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
Measure Participants	0	0

Adverse Events

Time Frame	up to approximately 12 months
Adverse Event Reporting Description	The safety population included all subjects enrolled in the study who received at least 1 dose of study treatment.
Arm/Group Title	INCB001158 50mg BID+ Epacadostat + Pembrolizumab		INCB001158 75 mg BID + Epacadostat + Pembrolizumab
Arm/Group Description	INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W)		INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W)
All Cause Mortality
	INCB001158 50mg BID+ Epacadostat + Pembrolizumab		INCB001158 75 mg BID + Epacadostat + Pembrolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		0/1 (0%)
Serious Adverse Events
	INCB001158 50mg BID+ Epacadostat + Pembrolizumab		INCB001158 75 mg BID + Epacadostat + Pembrolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		1/1 (100%)
Cardiac disorders
Myocardial infarction	1/4 (25%)		0/1 (0%)
Infections and infestations
Clostridium difficile infection	1/4 (25%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/4 (25%)		0/1 (0%)
Nervous system disorders
Ataxia	0/4 (0%)		1/1 (100%)
Brain oedema	0/4 (0%)		1/1 (100%)
Renal and urinary disorders
Hydronephrosis	1/4 (25%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	INCB001158 50mg BID+ Epacadostat + Pembrolizumab		INCB001158 75 mg BID + Epacadostat + Pembrolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		0/1 (0%)
Eye disorders
Dry eye	1/4 (25%)		0/1 (0%)
Gastrointestinal disorders
Abdominal pain lower	1/4 (25%)		0/1 (0%)
Abdominal pain upper	1/4 (25%)		0/1 (0%)
Constipation	1/4 (25%)		0/1 (0%)
Diarrhoea	2/4 (50%)		0/1 (0%)
Dry mouth	1/4 (25%)		0/1 (0%)
Nausea	1/4 (25%)		0/1 (0%)
Vomiting	1/4 (25%)		0/1 (0%)
General disorders
Chills	1/4 (25%)		0/1 (0%)
Fatigue	2/4 (50%)		0/1 (0%)
Non-cardiac chest pain	1/4 (25%)		0/1 (0%)
Peripheral swelling	1/4 (25%)		0/1 (0%)
Pyrexia	2/4 (50%)		0/1 (0%)
Infections and infestations
Oral herpes	1/4 (25%)		0/1 (0%)
Urinary tract infection	1/4 (25%)		0/1 (0%)
Investigations
Weight increased	1/4 (25%)		0/1 (0%)
White blood cell count decreased	1/4 (25%)		0/1 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/4 (25%)		0/1 (0%)
Hypercalcaemia	1/4 (25%)		0/1 (0%)
Hyperkalaemia	1/4 (25%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Flank pain	1/4 (25%)		0/1 (0%)
Limb discomfort	1/4 (25%)		0/1 (0%)
Pain in extremity	1/4 (25%)		0/1 (0%)
Nervous system disorders
Dysgeusia	1/4 (25%)		0/1 (0%)
Renal and urinary disorders
Pollakiuria	1/4 (25%)		0/1 (0%)
Urinary tract obstruction	1/4 (25%)		0/1 (0%)
Reproductive system and breast disorders
Vaginal discharge	1/4 (25%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/4 (25%)		0/1 (0%)
Oropharyngeal pain	1/4 (25%)		0/1 (0%)
Rhinitis allergic	1/4 (25%)		0/1 (0%)
Wheezing	1/4 (25%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Erythema	1/4 (25%)		0/1 (0%)
Pruritus	1/4 (25%)		0/1 (0%)
Rash	1/4 (25%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Clinical Study Agreement