INCAGN01876 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies
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 |
---|---|---|
Phase 1/Phase 2 |
Study Design
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:
Drug: Pembrolizumab
Pembrolizumab will be administered IV at the protocol-defined dose.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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
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)
More Information
Publications
None provided.- INCAGN 1876-202
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
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%
|
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%
|
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 |
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%
|
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
|
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
|
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
|
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 | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
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
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Clinical Study Agreement
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Incyte Corporation |
Phone | 1-855-463-3463 |
medinfo@incyte.com |
- INCAGN 1876-202