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A Study of INCAGN01876 in Participants With Advanced or Metastatic Solid Tumors

Primary Purpose

Advanced Malignancies, Metastatic Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
INCAGN01876
Sponsored by
Incyte Biosciences International Sàrl
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Malignancies focused on measuring Solid tumor, adenocarcinoma of the endometrium, melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), glucocorticoid-induced tumor necrosis factor receptor (GITR)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Sites / Locations

  • The Angeles Clinic and Research Institute
  • Yale University
  • Beth Israel Deaconess Medical Center
  • Dana Farber Cancer Institute
  • Memorial Sloan Kettering at Monmouth
  • MSK Westchester
  • Memorial Sloan Kettering Cancer Center
  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

Phase 1: 0.03 mg/kg Q2W

Phase 1: 0.1 mg/kg Q2W

Phase 1: 0.3 mg/kg Q2W

Phase 1: 1.0 mg/kg Q2W

Phase 1: 3.0 mg/kg Q2W

Phase 1: 5.0 mg/kg Q2W

Phase 1: 10.0 mg/kg Q2W

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

Phase 2: 300 mg/kg Q2W

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Maximum Observed Plasma Concentration (Cmax)
Time to Maximum Concentration (Tmax)
Minimum Observed Plasma Concentration Over the Dose Interval (Cmin)
Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t)
Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST)
ORR is defined as the percentage of participants having complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease assessments. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
Duration of Response (DOR) Per RECIST and mRECIST
DOR is defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
Duration of Disease Control Per RECIST and mRECIST
Duration of disease control (CR, PR, and stable disease [SD]), as measured from first report of SD or better until disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Progression Free Survival (PFS) Per RECIST and mRECIST
PFS is defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. Progression is defined by RECIST and mRECIST as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute lesion increase of at least 5 mm or the appearance of new lesions.

Full Information

First Posted
February 22, 2016
Last Updated
February 9, 2021
Sponsor
Incyte Biosciences International Sàrl
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1. Study Identification

Unique Protocol Identification Number
NCT02697591
Brief Title
A Study of INCAGN01876 in Participants With Advanced or Metastatic Solid Tumors
Official Title
A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN01876 in Subjects With Advanced or Metastatic Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
June 20, 2016 (Actual)
Primary Completion Date
December 16, 2019 (Actual)
Study Completion Date
December 16, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Biosciences International Sàrl

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Malignancies, Metastatic Cancer
Keywords
Solid tumor, adenocarcinoma of the endometrium, melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), glucocorticoid-induced tumor necrosis factor receptor (GITR)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1: 20.0 Milligram Per Kilograms (mg/kg) Every 2 Weeks (Q2W)
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: 0.03 mg/kg Q2W
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: 0.1 mg/kg Q2W
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: 0.3 mg/kg Q2W
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: 1.0 mg/kg Q2W
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: 3.0 mg/kg Q2W
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: 5.0 mg/kg Q2W
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: 10.0 mg/kg Q2W
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1: 400 mg/kg Every 4 Weeks (Q4W)
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2: 300 mg/kg Q2W
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
INCAGN01876
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity
Description
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.
Time Frame
From screening through 60 days after end of treatment, up to Month 15
Secondary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax)
Time Frame
Day 1 of Cycles 1 and 6 post-dose
Title
Time to Maximum Concentration (Tmax)
Time Frame
Day 1 of Cycles 1 and 6 post-dose
Title
Minimum Observed Plasma Concentration Over the Dose Interval (Cmin)
Time Frame
Day 1 of Cycles 2, 3, 4, 6, and 7 post-dose
Title
Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t)
Time Frame
Day 1 of Cycles 1 and 6 post-dose
Title
Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST)
Description
ORR is defined as the percentage of participants having complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease assessments. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
Time Frame
Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
Title
Duration of Response (DOR) Per RECIST and mRECIST
Description
DOR is defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
Time Frame
Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
Title
Duration of Disease Control Per RECIST and mRECIST
Description
Duration of disease control (CR, PR, and stable disease [SD]), as measured from first report of SD or better until disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame
Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
Title
Progression Free Survival (PFS) Per RECIST and mRECIST
Description
PFS is defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. Progression is defined by RECIST and mRECIST as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute lesion increase of at least 5 mm or the appearance of new lesions.
Time Frame
Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Janik, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
Facility Name
The Angeles Clinic and Research Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Memorial Sloan Kettering at Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
MSK Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study of INCAGN01876 in Participants With Advanced or Metastatic Solid Tumors

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