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Advanced MalignanciesPhase 1/2NCT03241173

A Study Exploring the Safety and Efficacy of INCAGN01949 in Combination With Immune Therapies in Advanced or Metastatic Malignancies

A Phase 1/2 study testing INCAGN01949, Nivolumab and Ipilimumab in people with Advanced Malignancies, run by Incyte Biosciences International Sàrl at 15 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

The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01949 when given in combination with immune therapies in participants with advanced or metastatic malignancies. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Malignancies
What is being tested?
INCAGN01949, Nivolumab and Ipilimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
15 sitesUnited States
Study dates
9 Oct 2017to 17 Sep 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.
  • Phase 1: Subjects with advanced or metastatic solid tumors.
  • Phase 1: Subjects who have disease progression after treatment with available therapies.
  • Phase 2: Subjects with advanced or metastatic gastric cancer, SCCHN, NSCLC, or RCC and are considered refractory to prior PD-1/L1 therapy.
  • Presence of measurable disease based on 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.
  • Active autoimmune disease.
  • Known active central nervous system metastases and/or carcinomatous meningitis.
  • Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
  • Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
  • Known history of human immunodeficiency virus (HIV); HIV 1/2 antibodies.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites
  • University of Michigan

    Ann Arbor, Michigan, 48109

  • The University of Alabama Birmingham (UAB)

    Birmingham, Alabama, 90025

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • John Theurer Cancer Center At Hackensack UMC

    Hackensack, New Jersey, 07601

  • Carolina BioOncology Institute

    Huntersville, North Carolina, 28078

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • Mount Sinai Medical Center of Florida, Inc.

    Miami, Florida, 33140

  • Sarah Cannon Research Institute, LLC (SCRI)

    Nashville, Tennessee, 37203

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Rutgers, The State University

    New Brunswick, New Jersey, 08901

  • New York University Clinical Cancer Center

    New York, New York, 10016

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • Scottsdale Healthcare Hospitals DBA HonorHealth

    Scottsdale, Arizona, 85258

Other trials in United States

About this study

Official title: A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01949 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies

The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01949 when given in combination with immune therapies in participants with advanced or metastatic malignancies.

Being tested
INCAGN01949, Nivolumab, Ipilimumab
Keywords
advanced or metastatic cervical cancer, endometrial cancer, esophageal cancer, hepatocellular carcinoma (HCC), melanoma, Merkel cell carcinoma, mesothelioma, microsatellite instability-high colorectal cancer, non-small cell lung cancer (NSCLC), ovarian cancer, squamous cell carcinoma of the head and neck, small cell lung cancer (SLCL), renal cell carcinoma (RCC), triple-negative breast cancer, TNBC, urothelial carcinoma, OX40 ligand (OX40), SCCHN, MSI-H CRC, gastric cancer (including stomach and gastroesophageal junction [GEJ])
Medical subject headings
Uterine Cervical Neoplasms, Endometrial Neoplasms, Esophageal Neoplasms, Carcinoma, Hepatocellular, Melanoma, Carcinoma, Merkel Cell, Mesothelioma, Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • INCAGN01949Drug

    In Phase 1, participants will receive INCAGN01949 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will receive INCAGN01949 administered IV at the recommended dose from Phase 1.

  • NivolumabDrug

    Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

  • IpilimumabDrug

    Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Study groups in NCT03241173
Study groupRoleWhat they receive
Phase 1, Dose Escalation: INCAGN01949 + NivolumabExperimentalINCAGN01949 (70, 200, 350, or 700 milligrams [mg]) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors
Receives: Drug: INCAGN01949; Drug: Nivolumab
Phase 1, Dose Escalation: INCAGN01949 + IpilimumabExperimentalINCAGN01949 (70, 200, 350, or 700 mg) combined with ipilimumab 1 mg/kilogram (kg) in participants with advanced or metastatic select solid tumors
Receives: Drug: INCAGN01949; Drug: Ipilimumab
Phase 1, Dose Escalation: INCAGN01949 + Nivolumab + IpilimumabExperimentalINCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors
Receives: Drug: INCAGN01949; Drug: Nivolumab; Drug: Ipilimumab
Phase 1, Safety Expansion: INCAGN01949 + NivolumabExperimentalRun-in with INCAGN01949 (70, 200, or 350 mg) x 2 doses, followed by INCAGN01949 (70, 200, or 350 mg) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors
Receives: Drug: INCAGN01949; Drug: Nivolumab
Phase 1, Safety Expansion: INCAGN01949 + Nivolumab + IpilimumabExperimentalRun-in with INCAGN01949 x 2 doses, followed by INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors
Receives: Drug: INCAGN01949; Drug: Nivolumab; Drug: Ipilimumab
Phase 2, Part A: INCAGN01949 + nivolumabExperimentalINCAGN01949 combined with nivolumab in programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) refractory participants with gastric cancer, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC)
Receives: Drug: INCAGN01949; Drug: Nivolumab
Phase 2, Part B: INCAGN01949; INCAGN01949 + nivolumab; INCAGN01949 + nivolumab + ipilimumabExperimentalINCAGN01949 alone, combined with nivolumab, and combined with nivolumab and ipilimumab in PD-1/L1 refractory participants with advanced or metastatic gastric cancer, SCCHN, NSCLC, or RCC
Receives: Drug: INCAGN01949; Drug: Nivolumab; Drug: Ipilimumab

What is being measured

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

  1. Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    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 that occurred 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 adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.

    Measured: up to 17.4 months

  2. Phase 1: Number of Participants With a Grade 3 or Higher TEAE

    An 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. A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death due to AE.

    Measured: up to 17.4 months

  3. Phase 2: Objective Response Rate (ORR)

    ORR was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by investigator assessment of radiographic disease assessments, recorded before and including the first event of progressive disease (PD). 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.

    Measured: up to 24 months

Secondary outcomes (11)
  1. Phase 1: ORR

    ORR was defined as the percentage of participants with a confirmed best overall response of CR or PR, per RECIST v1.1, as determined by investigator assessment of radiographic disease assessments, recorded before and including the first event of PD. 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 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.

    Measured: up to 15.6 months

  2. Phase 1: Duration of Response (DOR)

    DOR was defined as the time from the first overall response contributing to a confirmed objective response (CR or PR) to the earlier of the participant's death from any cause or first assessment of PD, determined by investigator assessment of radiographic disease assessments per RECIST 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 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. PD: progression of a target or non-target lesion or presence of a new lesion.

    Measured: up to 11.0 months

  3. Phase 2: DOR

    DOR was defined as the time from the first overall response contributing to a confirmed objective response (CR or PR) to the earlier of the participant's death from any cause or first assessment of PD, determined by investigator assessment of radiographic disease assessments per RECIST 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 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. PD: progression of a target or non-target lesion or presence of a new lesion.

    Measured: up to 24 months

  4. Phase 1: Disease Control Rate (DCR)

    DCR was defined as the percentage of participants with a CR, PR, or stable disease (SD), determined by investigator assessment of radiographic disease assessments per RECIST 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 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. SD: no change in target lesions to qualify for CR, PR, or PD.

    Measured: up to 15.6 months

  5. Phase 2: DCR

    DCR was defined as the percentage of participants with a CR, PR, or SD, determined by investigator assessment of radiographic disease assessments per RECIST 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 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. SD: no change in target lesions to qualify for CR, PR, or PD.

    Measured: up to 24 months

  6. Phase 1: Duration of Disease Control

    Duration of disease control (CR, PR, and SD) was measured from the first report of SD or better until PD or death from any cause, if occurring sooner than progression, determined by investigator assessment of radiographic disease assessments per RECIST 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 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. SD: no change in target lesions to qualify for CR, PR, or PD. PD: progression of a target or non-target lesion or presence of a new lesion.

    Measured: up to 15.4 months

  7. Phase 2: Duration of Disease Control

    Duration of disease control (CR, PR, and SD) was measured from the first report of SD or better until PD or death from any cause, if occurring sooner than progression, determined by investigator assessment of radiographic disease assessments per RECIST 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 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. SD: no change in target lesions to qualify for CR, PR, or PD. PD: progression of a target or non-target lesion or presence of a new lesion.

    Measured: up to 24 months

  8. Phase 1: Progression-free Survival (PFS)

    PFS was defined as the length of time between the Baseline visit (Day 1) and the earlier of death or the first assessment of PD, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1.

    Measured: up to 15.6 months

  9. Phase 2: PFS

    PFS was defined as the length of time between the Baseline visit (Day 1) and the earlier of death or the first assessment of PD, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1.

    Measured: up to 24 months

  10. Phase 2: Number of Participants With TEAEs

    An 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 that occurred 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 adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.

    Measured: up to 24 months

  11. Phase 2: Number of Participants With a Grade 3 or Higher TEAE

    An 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. A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using CTCAE v4.03. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death due to AE.

    Measured: up to 24 months

Timeline

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

  1. First posted7 Aug 2017
  2. Study start9 Oct 2017
  3. Primary completion17 Sep 2019
  4. Study completion17 Sep 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
Parallel groups
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03241173
Sponsor's protocol ID
INCAGN 1949-201
Status last verified
Sep 2022
First submitted
2 Aug 2017
Last updated
27 Sep 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing INCAGN01949, Nivolumab and Ipilimumab in people with Advanced Malignancies, run by Incyte Biosciences International Sàrl at 15 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 8 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 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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 27 Sep 2022). 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?

Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: up to 17.4 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 27 Sep 2022.

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