NCT03314935

Brief Summary

The purpose of this open-label nonrandomized Phase 1/2 study is to evaluate INCB001158 in combination with chemotherapy in participants with advanced/metastatic solid tumors.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
149

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2017

Longer than P75 for phase_1

Geographic Reach
3 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 16, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 19, 2017

Completed
1 month until next milestone

Study Start

First participant enrolled

November 21, 2017

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 28, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 28, 2022

Completed
1 year until next milestone

Results Posted

Study results publicly available

December 7, 2023

Completed
Last Updated

August 12, 2025

Status Verified

August 1, 2025

Enrollment Period

5 years

First QC Date

October 16, 2017

Results QC Date

October 10, 2023

Last Update Submit

August 8, 2025

Conditions

Keywords

INCB001158arginase inhibitoroxaliplatinleucovorin5 fluorouracilgemcitabinecisplatinpaclitaxelsolid tumorscolorectal cancerbiliary tract cancergastroesophageal cancerendometrial cancerovarian cancer

Outcome Measures

Primary Outcomes (4)

  • Phases 1 and 2: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

    An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.

    up to 1385 days

  • Phase 1: Number of Participants With Any Dose-limiting Toxicity (DLT)

    A DLT was defined as the occurrence of any protocol-defined toxicity occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria.

    up to Day 28

  • Recommended Phase 2 Dose (RP2D) of INCB001158 When Given in Combination With Each Chemotherapy Regimen

    The RP2D of the combination of INCB001158 and chemotherapy in 21-day (for gemcitabine/cisplatin) or 28-day (for mFOLFOX6 or paclitaxel) treatment cycles in participants with advanced or metastatic solid tumors was determined. After the dose escalation was completed, the INCB001158 dose level that was pharmacologically active and tolerable in combination with each chemotherapy regimen (i.e., maximum tolerated dose or lower) was determined to be the RP2D. The RP2D was then further assessed in tumor expansion cohorts in Phase 2.

    up to Day 580

  • Phase 2: Objective Response Rate (ORR)

    ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Analysis was conducted by cohort (tumor type) in Phase 2 because different tumor types could have different response criteria or different background response rates.

    up to 1385 days

Secondary Outcomes (9)

  • Phase 1: ORR

    up to 580 days

  • Phases 1 and 2: Duration of Response

    up to 368 days

  • Phases 1 and 2: Disease Control Rate

    up to 1385 days

  • Phases 1 and 2: Progression-free Survival

    up to 1385 days

  • Cmin of INCB001158 in Participants Treated With INCB001158 in Combination With Chemotherapy on Cycle 2 Day 1 Following Repeated Dose Administration

    Day 1 of Cycle 2: predose; 0.5, 1, 2, 4, 6, and 8-10 hours post-dose for extensive sample collection. Day 1 of Cycle 2: predose; 1 and 4 hours post-dose for sparse sample collection

  • +4 more secondary outcomes

Study Arms (3)

Treatment Group A

EXPERIMENTAL

INCB001158 + FOLFOX

Drug: INCB001158Drug: OxaliplatinDrug: LeucovorinDrug: 5-Fluorouracil

Treatment Group B

EXPERIMENTAL

INCB001158 + gemcitabine/cisplatin

Drug: INCB001158Drug: GemcitabineDrug: Cisplatin

Treatment Group C

EXPERIMENTAL

INCB001158 + paclitaxel

Drug: INCB001158Drug: Paclitaxel

Interventions

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.

Also known as: Arginase inhibitor
Treatment Group ATreatment Group BTreatment Group C

Oxaliplatin administered intravenously at the protocol-defined dose and schedule.

Treatment Group A

Leucovorin at the protocol-defined dose and regimen.

Treatment Group A

5-Fluorouracil at the protocol-defined dose and regimen.

Treatment Group A

Gemcitabine at the protocol-defined dose and regimen.

Treatment Group B

Cisplatin at the protocol-defined dose and regimen.

Treatment Group B

Paclitaxel at the protocol-defined dose and regimen.

Treatment Group C

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors.
  • Presence of measurable disease per RECIST v1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Baseline archival tumor specimen available or willingness to undergo a pretreatment tumor biopsy to obtain the specimen.
  • Resolution of treatment-related toxicities.
  • Adequate hepatic, renal, cardiac, and hematologic function.
  • Additional cohort-specific criteria may apply.

You may not qualify if:

  • Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose.
  • Has received a prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before administration of study drug.
  • Has had prior chemotherapy or targeted small molecule therapy within 2 weeks before administration of study treatment.
  • Has received prior approved radiotherapy within 14 days of study therapy.
  • Has had known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years.
  • Has an active infection requiring systemic therapy.
  • Has known active CNS metastases and/or carcinomatous meningitis.
  • Women who are pregnant or breastfeeding.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

University of Alabama

Birmingham, Alabama, 35294-3300, United States

Location

USA Mitchell Cancer Center

Mobile, Alabama, 36604, United States

Location

UC Davis - Comprehensive Cancer Centre

Sacramento, California, 95817, United States

Location

Northwest Georgia Oncology Centers

Marietta, Georgia, 30060, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

START San Antonio

San Antonio, Texas, 78229, United States

Location

Grand Hopital de Charleroi - Department of Medical Oncology

Brussels, 6000, Belgium

Location

Institut Jules Bordet - Clinical Trials Conduct Unit

Brussels, B-1000, Belgium

Location

UCL Cancer Institute

London, WC1E 6BT, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

  • Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.

MeSH Terms

Conditions

Biliary Tract NeoplasmsColorectal NeoplasmsEndometrial NeoplasmsOvarian Neoplasms

Interventions

OxaliplatinLeucovorinFluorouracilGemcitabineCisplatinPaclitaxel

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsBiliary Tract DiseasesDigestive System DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesUterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsCoenzymesEnzymes and CoenzymesUracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingDeoxycytidineCytidinePyrimidine NucleosidesChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsDiterpenesTerpenes

Results Point of Contact

Title
Study Director
Organization
Incyte Corporation

Study Officials

  • Lance Leopold, MD

    Incyte Corporation

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 16, 2017

First Posted

October 19, 2017

Study Start

November 21, 2017

Primary Completion

November 28, 2022

Study Completion

November 28, 2022

Last Updated

August 12, 2025

Results First Posted

December 7, 2023

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will share

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
Access Criteria
Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
More information

Locations