NCT02697591

Brief Summary

This was an open-label, non-randomized Phase 1/2 safety study of INCAGN01876 in participants with advanced or metastatic solid tumors that was conducted in 2 parts. Part 1 is dose escalation and safety expansion which determines the optimal dose and maximum number of tolerated doses. Part 2 is dose expansion in which Part 1 recommended dose will be evaluated.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
100

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jun 2016

Typical duration for phase_1

Geographic Reach
1 country

8 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

February 22, 2016

Completed
10 days until next milestone

First Posted

Study publicly available on registry

March 3, 2016

Completed
4 months until next milestone

Study Start

First participant enrolled

June 20, 2016

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 16, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 16, 2019

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

February 26, 2021

Completed
Last Updated

February 26, 2021

Status Verified

February 1, 2021

Enrollment Period

3.5 years

First QC Date

February 22, 2016

Results QC Date

December 16, 2020

Last Update Submit

February 9, 2021

Conditions

Keywords

Solid tumoradenocarcinoma of the endometriummelanoma, non-small cell lung cancer (NSCLC)renal cell carcinoma (RCC)glucocorticoid-induced tumor necrosis factor receptor (GITR)

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity

    AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent AE is any AE either reported for first time or worsening of a pre-existing event after the first dose of study drug. Grade 1 AEs is defined as Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 AEs is defined as Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3 AEs is defined as the severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living and Grade 4 AEs as life-threatening consequences; urgent intervention indicated. Data is reported for Grade 3 and higher severity for this outcome measure.

    From screening through 60 days after end of treatment, up to Month 15

Secondary Outcomes (8)

  • Maximum Observed Plasma Concentration (Cmax)

    Day 1 of Cycles 1 and 6 post-dose

  • Time to Maximum Concentration (Tmax)

    Day 1 of Cycles 1 and 6 post-dose

  • Minimum Observed Plasma Concentration Over the Dose Interval (Cmin)

    Day 1 of Cycles 2, 3, 4, 6, and 7 post-dose

  • Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t)

    Day 1 of Cycles 1 and 6 post-dose

  • Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST)

    Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months

  • +3 more secondary outcomes

Study Arms (10)

Phase 1: 20.0 Milligram Per Kilograms (mg/kg) Every 2 Weeks (Q2W)

EXPERIMENTAL

Participants received IV infusion of study drug at a dose of 20.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Phase 1: 0.03 mg/kg Q2W

EXPERIMENTAL

Participants received intravenous (IV) infusion of study drug at a dose of 0.03 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Phase 1: 0.1 mg/kg Q2W

EXPERIMENTAL

Participants received IV infusion of study drug at a dose of 0.1 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Phase 1: 0.3 mg/kg Q2W

EXPERIMENTAL

Participants received IV infusion of study drug at a dose of 0.3 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Phase 1: 1.0 mg/kg Q2W

EXPERIMENTAL

Participants received IV infusion of study drug at a dose of 1.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Phase 1: 3.0 mg/kg Q2W

EXPERIMENTAL

Participants received IV infusion of study drug at a dose of 3.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Phase 1: 5.0 mg/kg Q2W

EXPERIMENTAL

Participants received IV infusion of study drug at a dose of 5.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Phase 1: 10.0 mg/kg Q2W

EXPERIMENTAL

Participants received IV infusion of study drug at a dose of 10.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Phase 1: 400 mg/kg Every 4 Weeks (Q4W)

EXPERIMENTAL

Participants received IV infusion of study drug at a dose of 400 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Phase 2: 300 mg/kg Q2W

EXPERIMENTAL

Participants received IV infusion of study drug at a dose of 300 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Drug: INCAGN01876

Interventions

Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.

Phase 1: 0.03 mg/kg Q2WPhase 1: 0.1 mg/kg Q2WPhase 1: 0.3 mg/kg Q2WPhase 1: 1.0 mg/kg Q2WPhase 1: 10.0 mg/kg Q2WPhase 1: 20.0 Milligram Per Kilograms (mg/kg) Every 2 Weeks (Q2W)Phase 1: 3.0 mg/kg Q2WPhase 1: 400 mg/kg Every 4 Weeks (Q4W)Phase 1: 5.0 mg/kg Q2WPhase 2: 300 mg/kg Q2W

Eligibility Criteria

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

You may qualify if:

  • Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
  • Part 1: Participants with advanced or metastatic solid tumors.
  • Part 2: Participants with advanced or metastatic adenocarcinoma of endometrium, melanoma, non-small cell lung cancer, and renal cell carcinoma.
  • Participants who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or participants who refuse standard treatment.
  • Presence of measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

You may not qualify if:

  • Laboratory and medical history parameters not within the protocol-defined range.
  • 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 and/or complications from prior surgical intervention before starting therapy.
  • Receipt of a live vaccine within 30 days of planned start of study therapy.
  • Active autoimmune disease.
  • Prior treatment with any tumor necrosis factor super family agonist.
  • Known active central nervous system metastases and/or carcinomatous meningitis.
  • Evidence of active, non-infectious pneumonitis or history of interstitial lung disease.
  • Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering at Monmouth

Middletown, New Jersey, 07748, United States

Location

MSK Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

  • Hamid O, Cardin DB, Hodi FS, LoRusso P, Merghoub T, Zappasodi R, Maniyar R, Janik JE, van der Velden MVW, Zhou F, Dong Z, Chen X, Harding JJ. First-in-Human Phase I/II Study of INCAGN01876, a Glucocorticoid-Induced Tumor Necrosis Factor Receptor Agonist, in Patients with Advanced or Metastatic Solid Tumors. Clin Cancer Res. 2025 Oct 1;31(19):4089-4100. doi: 10.1158/1078-0432.CCR-24-4141.

MeSH Terms

Conditions

Neoplasm MetastasisMelanomaCarcinoma, Non-Small-Cell LungCarcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Neoplastic ProcessesNeoplasmsPathologic ProcessesPathological Conditions, Signs and SymptomsNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Results Point of Contact

Title
Study Director
Organization
Incyte Corporation

Study Officials

  • John Janik, 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

February 22, 2016

First Posted

March 3, 2016

Study Start

June 20, 2016

Primary Completion

December 16, 2019

Study Completion

December 16, 2019

Last Updated

February 26, 2021

Results First Posted

February 26, 2021

Record last verified: 2021-02

Data Sharing

IPD Sharing
Will not share

Locations