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

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN01876 in Subjects With Advanced or Metastatic Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer; Advanced Malignancies
• Intervention / Treatment: Drug: INCAGN01876

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering at Monmouth
  • New York
    • Harrison, New York, United States, 10604
      • MSK Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: 20.0 Milligram Per Kilograms (mg/kg) Every 2 Weeks (Q2W); 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; 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.
Experimental: Phase 1: 0.03 mg/kg Q2W; 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; 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.
Experimental: Phase 1: 0.1 mg/kg Q2W; 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; 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.
Experimental: Phase 1: 0.3 mg/kg Q2W; 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; 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.
Experimental: Phase 1: 1.0 mg/kg Q2W; 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; 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.
Experimental: Phase 1: 3.0 mg/kg Q2W; 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; 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.
Experimental: Phase 1: 5.0 mg/kg Q2W; 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; 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.
Experimental: Phase 1: 10.0 mg/kg Q2W; 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; 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.
Experimental: Phase 1: 400 mg/kg Every 4 Weeks (Q4W); 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; 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.
Experimental: Phase 2: 300 mg/kg Q2W; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
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.	Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
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.	Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months
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.	Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months

Collaborators and Investigators

• Sponsor: Incyte Biosciences International Sàrl

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2016
• Primary Completion (Actual): December 16, 2019
• Study Completion (Actual): December 16, 2019

Study Registration Dates

• First Submitted: February 22, 2016
• First Submitted That Met QC Criteria: February 26, 2016
• First Posted (Estimate): March 3, 2016

Study Record Updates

• Last Update Posted (Actual): February 26, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• 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)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: INCAGN 1876-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No