INCAGN01876 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies

• Sponsor: Incyte Biosciences International Sàrl (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03277352
• Collaborator: (none)
• Enrollment: 10
• Locations: 2
• Arm: 1
• Actual Duration (Months): 31.3
• Patients Per Site: 5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01876 when given in combination with immune therapies.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancies; Metastatic Cancer	Drug: INCAGN01876; Drug: Epacadostat; Drug: Pembrolizumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Safety and Efficacy Study of INCAGN01876 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies
• Actual Study Start Date: Nov 21, 2017
• Actual Primary Completion Date: Jul 1, 2020
• Actual Study Completion Date: Jul 1, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: INCAGN01876 + Pembrolizumab + Epacadostat INCAGN01876 in combination with pembrolizumab and epacadostat

Drug: INCAGN01876; In Phase 1 subjects will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose and schedule according to cohort and treatment group enrollment. In Phase 2, subjects will be administered IV study drug at the recommended dose from Phase 1.; Drug: Epacadostat; Epacadostat will be self-administered orally at the protocol-defined dose.; Other Names: INCB024360 ; Drug: Pembrolizumab; Pembrolizumab will be administered IV at the protocol-defined dose.; Other Names: Keytruda®

Outcome Measures

Primary Outcome Measures

1. Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] [Screening through 60 days after end of treatment, up to approximately 18 months]

   A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment.

2. Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]

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

3. Phase 2: Complete Response Rate (CRR) Based on RECIST v1.1 [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]

   Defined as the percentage of checkpoint inhibitor-naive melanoma participants who have a CR based on investigator assessment per RECIST v1.1

Secondary Outcome Measures

1. Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months.]

   Defined as the percentage of participants having CR, PR, or stable disease (SD) based on investigator assessment per RECIST v1.1.

2. Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]

   Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause.

3. Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]

   Defined as time from first report of SD or better until disease progression or death from any cause.

4. Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST [Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months]

   Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause.

5. Phase 1 & Phase 2: Overall Survival [At 1 year and 2 years.]

   Defined as the time from the start of combination therapy until death due to any cause.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.

• Phase 1: Subjects with advanced or metastatic solid tumors.

• Phase 1: Subjects who have disease progression after treatment with available therapies.

• Phase 2: Subjects with advanced or metastatic melanoma, RCC, and urothelial carcinoma.

• Presence of measurable disease based on RECIST v1.1.

• Eastern Cooperative Oncology Group performance status of 0 or 1.

Exclusion Criteria:

• Laboratory and medical history parameters not within the Protocol-defined range

• Prior treatment with any tumor necrosis factor super family agonist.

• Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.

• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy.

• Active autoimmune disease.

• Known active central nervous system metastases and/or carcinomatous meningitis.

• Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.

• Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

• Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Angeles Clinic and Research Institute	Los Angeles	California	United States	90025
2	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601

Sponsors and Collaborators

• Incyte Biosciences International Sàrl

Investigators

• Study Director: John N. Janik, MD, Incyte Corporation

Study Documents (Full-Text)

• Study Protocol - Aug 24, 2017
• Statistical Analysis Plan - Jun 1, 2018

More Information

Publications

None provided.

• Responsible Party: Incyte Biosciences International Sàrl
• ClinicalTrials.gov Identifier: NCT03277352
• Other Study ID Numbers: INCAGN 1876-202
• First Posted: Sep 11, 2017
• Last Update Posted: Jul 22, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Incyte Biosciences International Sàrl: cervical cancer; endometrial cancer; gastric cancer (including stomach and gastroesophageal junction (GEJ)); esophageal cancer; hepatocellular carcinoma (HCC); melanoma (mucosal or cutaneous); Merkel cell carcinoma; mesothelioma; microsatellite instability-high (MSI-H); solid tumors; non-small cell lung cancer (NSCLC); ovarian cancer; squamous cell carcinoma of the head and neck (SCCHN); small cell lung cancer (SCLC); renal cell carcinoma (RCC); triple-negative breast cancer (TNBC); urothelial carcinoma; glucocorticoid-induced tumor necrosis factor receptor (GITR)
• Additional relevant MeSH terms: Neoplasms; Pembrolizumab

Study Results

Participant Flow

Recruitment Details	The study was conducted at 2 different sites in USA. A total of 10 participants were enrolled in the study.
Pre-assignment Detail	A total of 10 participants were screened and enrolled in the study.

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Period Title: Overall Study
STARTED	10
COMPLETED	0
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.2 (13.73)
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	1 10%
Not Hispanic or Latino	9 90%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	8 80%
Asian	1 10%
Other	1 10%

Outcome Measures

1. Primary Outcome

Title	Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]
Description	A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
Time Frame	Screening through 60 days after end of treatment, up to approximately 18 months

Outcome Measure Data

Analysis Population Description

The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Measure Participants	10
Count of Participants [Participants]	10 100%

2. Primary Outcome

Title	Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST
Description	Defined as the percentage of participants having a CR or PR based on investigator assessment per RECIST v1.1.
Time Frame	Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months

Outcome Measure Data

Analysis Population Description

The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Measure Participants	10
Count of Participants [Participants]	3 30%

3. Primary Outcome

Title	Phase 2: Complete Response Rate (CRR) Based on RECIST v1.1
Description	Defined as the percentage of checkpoint inhibitor-naive melanoma participants who have a CR based on investigator assessment per RECIST v1.1
Time Frame	Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months

Outcome Measure Data

Analysis Population Description

The study was terminated early and no participants enrolled in Phase 2 of the study.

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Measure Participants	0

4. Secondary Outcome

Title	Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST
Description	Defined as the percentage of participants having CR, PR, or stable disease (SD) based on investigator assessment per RECIST v1.1.
Time Frame	Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months.

Outcome Measure Data

Analysis Population Description

The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Measure Participants	10
Count of Participants [Participants]	7 70%

5. Secondary Outcome

Title	Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST
Description	Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause.
Time Frame	Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months

Outcome Measure Data

Analysis Population Description

The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Measure Participants	10
Median (95% Confidence Interval) [days]	NA

6. Secondary Outcome

Title	Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST
Description	Defined as time from first report of SD or better until disease progression or death from any cause.
Time Frame	Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months

Outcome Measure Data

Analysis Population Description

The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Measure Participants	10
mRECIST	NA
RECIST	525

7. Secondary Outcome

Title	Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST
Description	Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause.
Time Frame	Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months

Outcome Measure Data

Analysis Population Description

The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Measure Participants	10
mRECIST	17.36
RECIST	4.20

8. Secondary Outcome

Title	Phase 1 & Phase 2: Overall Survival
Description	Defined as the time from the start of combination therapy until death due to any cause.
Time Frame	At 1 year and 2 years.

Outcome Measure Data

Analysis Population Description

The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.

Arm/Group Title	INCAGN01876 + Pembrolizumab + Epacadostat
Arm/Group Description	INCAGN01876 in combination with pembrolizumab and epacadostat
Measure Participants	10
Median (95% Confidence Interval) [months]	25.59

Adverse Events

Time Frame	up to 18 months
Arm/Group Title	INCAGN01876 300 mg Q3W + Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID		Total
Arm/Group Description	INCAGN01876 300 mg Q3W + Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID		Total
All Cause Mortality
	INCAGN01876 300 mg Q3W + Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		4/10 (40%)
Serious Adverse Events
	INCAGN01876 300 mg Q3W + Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		3/10 (30%)
Eye disorders
Uveitis	1/10 (10%)	1	1/10 (10%)	1
Gastrointestinal disorders
Colitis	1/10 (10%)	1	1/10 (10%)	1
Rectal haemorrhage	1/10 (10%)	1	1/10 (10%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/10 (10%)	1	1/10 (10%)	1
Myelodysplastic syndrome	1/10 (10%)	1	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	INCAGN01876 300 mg Q3W + Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Anaemia	1/10 (10%)	1	1/10 (10%)	1
Neutropenia	1/10 (10%)	1	1/10 (10%)	1
Thrombocytopenia	1/10 (10%)	1	1/10 (10%)	1
Endocrine disorders
Adrenal insufficiency	1/10 (10%)	1	1/10 (10%)	1
Eye disorders
Eye irritation	1/10 (10%)	1	1/10 (10%)	1
Macular hole	1/10 (10%)	1	1/10 (10%)	1
Gastrointestinal disorders
Abdominal pain	1/10 (10%)	1	1/10 (10%)	1
Aphthous ulcer	1/10 (10%)	1	1/10 (10%)	1
Constipation	2/10 (20%)	2	2/10 (20%)	2
Diarrhoea	1/10 (10%)	1	1/10 (10%)	1
Dysphagia	1/10 (10%)	1	1/10 (10%)	1
Melaena	1/10 (10%)	1	1/10 (10%)	1
Stomatitis	1/10 (10%)	1	1/10 (10%)	1
Vomiting	1/10 (10%)	1	1/10 (10%)	1
General disorders
Axillary pain	1/10 (10%)	1	1/10 (10%)	1
Fatigue	3/10 (30%)	4	3/10 (30%)	4
Non-cardiac chest pain	1/10 (10%)	1	1/10 (10%)	1
Oedema peripheral	1/10 (10%)	1	1/10 (10%)	1
Pyrexia	1/10 (10%)	1	1/10 (10%)	1
Immune system disorders
Drug hypersensitivity	1/10 (10%)	1	1/10 (10%)	1
Infections and infestations
Herpes zoster	1/10 (10%)	1	1/10 (10%)	1
Upper respiratory tract infection	1/10 (10%)	1	1/10 (10%)	1
Viral upper respiratory tract infection	1/10 (10%)	1	1/10 (10%)	1
Investigations
Aspartate aminotransferase increased	1/10 (10%)	1	1/10 (10%)	1
Gamma-glutamyltransferase increased	1/10 (10%)	1	1/10 (10%)	1
Hydrogen breath test abnormal	1/10 (10%)	1	1/10 (10%)	1
Lipase increased	2/10 (20%)	2	2/10 (20%)	2
Weight decreased	2/10 (20%)	2	2/10 (20%)	2
White blood cell count decreased	1/10 (10%)	1	1/10 (10%)	1
Metabolism and nutrition disorders
Decreased appetite	2/10 (20%)	2	2/10 (20%)	2
Hyperchloraemia	1/10 (10%)	1	1/10 (10%)	1
Hyperuricaemia	1/10 (10%)	1	1/10 (10%)	1
Hypomagnesaemia	2/10 (20%)	2	2/10 (20%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	2/10 (20%)	2	2/10 (20%)	2
Back pain	1/10 (10%)	1	1/10 (10%)	1
Neck pain	3/10 (30%)	3	3/10 (30%)	3
Osteonecrosis	1/10 (10%)	1	1/10 (10%)	1
Nervous system disorders
Dizziness	1/10 (10%)	1	1/10 (10%)	1
Headache	1/10 (10%)	1	1/10 (10%)	1
Renal and urinary disorders
Haematuria	1/10 (10%)	1	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/10 (10%)	1	1/10 (10%)	1
Dysphonia	1/10 (10%)	1	1/10 (10%)	1
Lung infiltration	1/10 (10%)	1	1/10 (10%)	1
Pneumonitis	1/10 (10%)	1	1/10 (10%)	1
Rhinorrhoea	1/10 (10%)	1	1/10 (10%)	1
Throat irritation	1/10 (10%)	1	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Pruritus	3/10 (30%)	4	3/10 (30%)	4
Rash	3/10 (30%)	3	3/10 (30%)	3
Rash generalised	2/10 (20%)	2	2/10 (20%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Clinical Study Agreement