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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03241173
Recruitment Status : Completed
First Posted : August 7, 2017
Results First Posted : September 27, 2022
Last Update Posted : September 27, 2022
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation ( Incyte Biosciences International Sàrl )

Brief 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.

Condition or disease Intervention/treatment Phase
Advanced Malignancies Drug: INCAGN01949 Drug: Nivolumab Drug: Ipilimumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 9, 2017
Actual Primary Completion Date : September 17, 2019
Actual Study Completion Date : September 17, 2019


Arm Intervention/treatment
Experimental: Phase 1, Dose Escalation: INCAGN01949 + Nivolumab
INCAGN01949 (70, 200, 350, or 700 milligrams [mg]) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors
Drug: INCAGN01949
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.

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

Experimental: Phase 1, Dose Escalation: INCAGN01949 + Ipilimumab
INCAGN01949 (70, 200, 350, or 700 mg) combined with ipilimumab 1 mg/kilogram (kg) in participants with advanced or metastatic select solid tumors
Drug: INCAGN01949
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.

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

Experimental: Phase 1, Dose Escalation: INCAGN01949 + Nivolumab + Ipilimumab
INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors
Drug: INCAGN01949
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.

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

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

Experimental: Phase 1, Safety Expansion: INCAGN01949 + Nivolumab
Run-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
Drug: INCAGN01949
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.

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

Experimental: Phase 1, Safety Expansion: INCAGN01949 + Nivolumab + Ipilimumab
Run-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
Drug: INCAGN01949
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.

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

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

Experimental: Phase 2, Part A: INCAGN01949 + nivolumab
INCAGN01949 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)
Drug: INCAGN01949
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.

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

Experimental: Phase 2, Part B: INCAGN01949; INCAGN01949 + nivolumab; INCAGN01949 + nivolumab + ipilimumab
INCAGN01949 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
Drug: INCAGN01949
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.

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

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




Primary Outcome Measures :
  1. Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: up to 17.4 months ]
    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.

  2. Phase 1: Number of Participants With a Grade 3 or Higher TEAE [ Time Frame: up to 17.4 months ]
    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.

  3. Phase 2: Objective Response Rate (ORR) [ Time Frame: up to 24 months ]
    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.


Secondary Outcome Measures :
  1. Phase 1: ORR [ Time Frame: up to 15.6 months ]
    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.

  2. Phase 1: Duration of Response (DOR) [ Time Frame: up to 11.0 months ]
    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.

  3. Phase 2: DOR [ Time Frame: up to 24 months ]
    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.

  4. Phase 1: Disease Control Rate (DCR) [ Time Frame: up to 15.6 months ]
    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.

  5. Phase 2: DCR [ Time Frame: up to 24 months ]
    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.

  6. Phase 1: Duration of Disease Control [ Time Frame: up to 15.4 months ]
    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.

  7. Phase 2: Duration of Disease Control [ Time Frame: up to 24 months ]
    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.

  8. Phase 1: Progression-free Survival (PFS) [ Time Frame: up to 15.6 months ]
    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.

  9. Phase 2: PFS [ Time Frame: up to 24 months ]
    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.

  10. Phase 2: Number of Participants With TEAEs [ Time Frame: up to 24 months ]
    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.

  11. Phase 2: Number of Participants With a Grade 3 or Higher TEAE [ Time Frame: up to 24 months ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03241173


Locations
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United States, Alabama
The University of Alabama Birmingham (UAB)
Birmingham, Alabama, United States, 90025
United States, Arizona
Scottsdale Healthcare Hospitals DBA HonorHealth
Scottsdale, Arizona, United States, 85258
United States, California
The Angeles Clinic and Research Institute
Los Angeles, California, United States, 90025
United States, Florida
Mount Sinai Medical Center of Florida, Inc.
Miami, Florida, United States, 33140
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New Jersey
John Theurer Cancer Center At Hackensack UMC
Hackensack, New Jersey, United States, 07601
Rutgers, The State University
New Brunswick, New Jersey, United States, 08901
United States, New York
New York University Clinical Cancer Center
New York, New York, United States, 10016
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Carolina BioOncology Institute
Huntersville, North Carolina, United States, 28078
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Sarah Cannon Research Institute, LLC (SCRI)
Nashville, Tennessee, United States, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Incyte Biosciences International Sàrl
Investigators
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Study Director: John E. Janik, MD Incyte Corporation
  Study Documents (Full-Text)

Documents provided by Incyte Corporation ( Incyte Biosciences International Sàrl ):
Study Protocol  [PDF] December 5, 2018
Statistical Analysis Plan  [PDF] February 6, 2018

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Responsible Party: Incyte Biosciences International Sàrl
ClinicalTrials.gov Identifier: NCT03241173    
Other Study ID Numbers: INCAGN 1949-201
First Posted: August 7, 2017    Key Record Dates
Results First Posted: September 27, 2022
Last Update Posted: September 27, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation ( Incyte Biosciences International Sàrl ):
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])
Additional relevant MeSH terms:
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Neoplasms
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action