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TerminatedNCT03277352Updated Jul 22, 2021Results posted

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

A Phase 1/2 interventional study of INCAGN01876 and Epacadostat in Advanced Malignancies and Metastatic Cancer, sponsored by Incyte Biosciences International Sàrl. Terminated at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-07-22.

Sponsored by Incyte Biosciences International Sàrl · Phase 1/2, Interventional, and Treatment

Why this study was terminated
The study was terminated due to emergent data from another study and unrelated to safety.
Phase
Phase 1/2
Study type
Interventional
Enrollment
10
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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

02

Conditions studied

  • Advanced Malignancies
  • Metastatic Cancer

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Keywords

  • 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)
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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).
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
10 participants (actual)

Study arms

  • Experimental
    INCAGN01876 + Pembrolizumab + Epacadostat

    INCAGN01876 in combination with pembrolizumab and epacadostat

    Drug: INCAGN01876 · Drug: Epacadostat · Drug: Pembrolizumab

Interventions

  • DrugINCAGN01876

    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.

  • DrugEpacadostat

    Epacadostat will be self-administered orally at the protocol-defined dose.

    Also known as: INCB024360

  • DrugPembrolizumab

    Pembrolizumab will be administered IV at the protocol-defined dose.

    Also known as: Keytruda®

05

What researchers measure

Primary outcomes

  1. Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]

    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

  2. Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST

    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

  3. Phase 2: Complete Response Rate (CRR) Based on RECIST v1.1

    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

Secondary outcomes

  1. Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST

    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.

  2. Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST

    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

  3. Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST

    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

  4. Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST

    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

  5. Phase 1 & Phase 2: Overall Survival

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

    Time frame: At 1 year and 2 years.

06

Results

Posted Jul 22, 2021

Participant flow

The study was conducted at 2 different sites in USA. A total of 10 participants were enrolled in the study.

Participant flow — Overall Study
MilestoneINCAGN01876 + Pembrolizumab + Epacadostat
Started10
Completed0
Not completed10
Withdrew: Study terminated by sponsor2
Withdrew: Withdrawal by subject4
Withdrew: Death4

Outcome measures

PrimaryPhase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]

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
Reported as:
Count of participants · Participants
Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]
ParticipantsINCAGN01876 + Pembrolizumab + Epacadostat
Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]10
PrimaryPhase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST

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
Reported as:
Count of participants · Participants
Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST
ParticipantsINCAGN01876 + Pembrolizumab + Epacadostat
Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST3
PrimaryPhase 2: Complete Response Rate (CRR) Based on RECIST v1.1

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

No measurements were reported for this outcome.

SecondaryPhase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST

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.
Reported as:
Count of participants · Participants
Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST
ParticipantsINCAGN01876 + Pembrolizumab + Epacadostat
Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST7
SecondaryPhase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST

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
Reported as:
Median · days
Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST
daysINCAGN01876 + Pembrolizumab + Epacadostat
Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECISTNA (273 to NA)
SecondaryPhase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST

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
Reported as:
Median · days
Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST
daysINCAGN01876 + Pembrolizumab + Epacadostat
mRECISTNA (525 to NA)
RECIST525 (92 to NA)
SecondaryPhase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST

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
Reported as:
Median · months
Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST
monthsINCAGN01876 + Pembrolizumab + Epacadostat
mRECIST17.36 (2.05 to NA)
RECIST4.20 (0.73 to NA)
SecondaryPhase 1 & Phase 2: Overall Survival

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

Time frame:
At 1 year and 2 years.
Reported as:
Median · months
Phase 1 & Phase 2: Overall Survival
monthsINCAGN01876 + Pembrolizumab + Epacadostat
Phase 1 & Phase 2: Overall Survival25.59 (16.76 to NA)

Adverse events

Collected over up to 18 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
INCAGN01876 300 mg Q3W + Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BID4/10 (40%)3/10 (30%)10/10 (100%)
Total4/10 (40%)3/10 (30%)10/10 (100%)
Most frequent serious events
Most frequent serious events
EventINCAGN01876 300 mg Q3W + Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BIDTotal
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/101/10
ColitisGastrointestinal disorders1/101/10
Myelodysplastic syndromeNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/101/10
Rectal haemorrhageGastrointestinal disorders1/101/10
UveitisEye disorders1/101/10
Most frequent other events
Showing 10 of 49
Most frequent other events
EventINCAGN01876 300 mg Q3W + Pembrolizumab 200 mg Q3W + Epacadostat 100 mg BIDTotal
FatigueGeneral disorders3/103/10
Neck painMusculoskeletal and connective tissue disorders3/103/10
PruritusSkin and subcutaneous tissue disorders3/103/10
RashSkin and subcutaneous tissue disorders3/103/10
ArthralgiaMusculoskeletal and connective tissue disorders2/102/10
ConstipationGastrointestinal disorders2/102/10
Decreased appetiteMetabolism and nutrition disorders2/102/10
HypomagnesaemiaMetabolism and nutrition disorders2/102/10
Lipase increasedInvestigations2/102/10
Rash generalisedSkin and subcutaneous tissue disorders2/102/10

Baseline characteristics

The Full Analysis Set (FAS) includes all subjects enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.

Age, Continuous
Age, Continuous(years)INCAGN01876 + Pembrolizumab + Epacadostat
Mean64.2 ± 13.73
Sex: Female, Male
Sex: Female, Male(Participants)INCAGN01876 + Pembrolizumab + Epacadostat
Female3
Male7
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)INCAGN01876 + Pembrolizumab + Epacadostat
Hispanic or Latino1
Not Hispanic or Latino9
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)INCAGN01876 + Pembrolizumab + Epacadostat
White/Caucasian8
Asian1
Other1
07

Study locations

2 sites
  • The Angeles Clinic and Research Institute
    Los Angeles, California 90025, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
08

References and documents

Study documents

  • Study protocol · Aug 24, 2017
  • Statistical analysis plan · Jun 1, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

09

Registry details

Key details

Study ID
NCT03277352
Lead sponsor
Incyte Biosciences International Sàrl
Responsible party
Sponsor
First posted
Sep 11, 2017
Start date
Nov 21, 2017
Primary completion
Jul 1, 2020
Completion
Jul 1, 2020
Results posted
Jul 22, 2021
Last update
Jul 22, 2021

Study contacts

John N. Janik, MD
study director · Incyte Corporation

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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