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Advanced MalignanciesPhase 1/2NCT02697591

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

A Phase 1/2 study testing INCAGN01876 in people with Advanced Malignancies and Metastatic Cancer, run by Incyte Biosciences International Sàrl at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Malignancies, Metastatic Cancer
What is being tested?
INCAGN01876
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
8 sitesUnited States
Study dates
20 Jun 2016to 16 Dec 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 9Show fewer
  • 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.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites
  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • MSK Westchester

    Harrison, New York, 10604

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • Memorial Sloan Kettering at Monmouth

    Middletown, New Jersey, 07748

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06511

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: 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.

Being tested
INCAGN01876
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)
Medical subject headings
Neoplasm Metastasis, Melanoma, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • INCAGN01876Drug

    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.

Study groups in NCT02697591
Study groupRoleWhat they receive
Phase 1: 20.0 Milligram Per Kilograms (mg/kg) Every 2 Weeks (Q2W)ExperimentalParticipants 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.
Receives: Drug: INCAGN01876
Phase 1: 0.03 mg/kg Q2WExperimentalParticipants 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.
Receives: Drug: INCAGN01876
Phase 1: 0.1 mg/kg Q2WExperimentalParticipants 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.
Receives: Drug: INCAGN01876
Phase 1: 0.3 mg/kg Q2WExperimentalParticipants 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.
Receives: Drug: INCAGN01876
Phase 1: 1.0 mg/kg Q2WExperimentalParticipants 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.
Receives: Drug: INCAGN01876
Phase 1: 3.0 mg/kg Q2WExperimentalParticipants 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.
Receives: Drug: INCAGN01876
Phase 1: 5.0 mg/kg Q2WExperimentalParticipants 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.
Receives: Drug: INCAGN01876
Phase 1: 10.0 mg/kg Q2WExperimentalParticipants 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.
Receives: Drug: INCAGN01876
Phase 1: 400 mg/kg Every 4 Weeks (Q4W)ExperimentalParticipants 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.
Receives: Drug: INCAGN01876
Phase 2: 300 mg/kg Q2WExperimentalParticipants 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.
Receives: Drug: INCAGN01876

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (8)
  1. Maximum Observed Plasma Concentration (Cmax)

    Measured: Day 1 of Cycles 1 and 6 post-dose

  2. Time to Maximum Concentration (Tmax)

    Measured: Day 1 of Cycles 1 and 6 post-dose

  3. Minimum Observed Plasma Concentration Over the Dose Interval (Cmin)

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

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

    Measured: Day 1 of Cycles 1 and 6 post-dose

  5. 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.

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

  6. 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.

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

  7. 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.

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

  8. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2016 (estimated)
  2. Study start20 Jun 2016
  3. Primary completion16 Dec 2019
  4. Study completion16 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02697591
Sponsor's protocol ID
INCAGN 1876-101
Status last verified
Feb 2021
First submitted
22 Feb 2016
Last updated
26 Feb 2021
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40711469

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing INCAGN01876 in people with Advanced Malignancies and Metastatic Cancer, run by Incyte Biosciences International Sàrl at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity (time frame: From screening through 60 days after end of treatment, up to Month 15). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02697591, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2021.

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