- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03241173
A Study Exploring the Safety and Efficacy of INCAGN01949 in Combination With Immune Therapies in Advanced or Metastatic Malignancies
September 9, 2022 updated by: Incyte Biosciences International Sàrl
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
52
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Alabama
-
Birmingham, Alabama, United States, 90025
- The University of Alabama Birmingham (UAB)
-
-
Arizona
-
Scottsdale, Arizona, United States, 85258
- Scottsdale Healthcare Hospitals DBA HonorHealth
-
-
California
-
Los Angeles, California, United States, 90025
- The Angeles Clinic and Research Institute
-
-
Florida
-
Miami, Florida, United States, 33140
- Mount Sinai Medical Center of Florida, Inc.
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- University of Michigan
-
Detroit, Michigan, United States, 48201
- Barbara Ann Karmanos Cancer Institute
-
-
New Jersey
-
Hackensack, New Jersey, United States, 07601
- John Theurer Cancer Center at Hackensack UMC
-
New Brunswick, New Jersey, United States, 08901
- Rutgers, the State University
-
-
New York
-
New York, New York, United States, 10016
- New York University Clinical Cancer Center
-
Rochester, New York, United States, 14642
- University of Rochester Medical Center
-
-
North Carolina
-
Huntersville, North Carolina, United States, 28078
- Carolina Biooncology Institute
-
-
Oregon
-
Portland, Oregon, United States, 97213
- Providence Portland Medical Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
-
Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute, LLC (SCRI)
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 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.
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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
|
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.
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
|
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.
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
|
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.
Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
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
|
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.
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
|
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.
Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
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)
|
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.
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
|
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.
Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
up to 17.4 months
|
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.
|
up to 17.4 months
|
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.
|
up to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
up to 15.6 months
|
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.
|
up to 11.0 months
|
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.
|
up to 24 months
|
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.
|
up to 15.6 months
|
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.
|
up to 24 months
|
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.
|
up to 15.4 months
|
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.
|
up to 24 months
|
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.
|
up to 15.6 months
|
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.
|
up to 24 months
|
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.
|
up to 24 months
|
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.
|
up to 24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: John E. Janik, MD, Incyte Corporation
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 9, 2017
Primary Completion (Actual)
September 17, 2019
Study Completion (Actual)
September 17, 2019
Study Registration Dates
First Submitted
August 2, 2017
First Submitted That Met QC Criteria
August 2, 2017
First Posted (Actual)
August 7, 2017
Study Record Updates
Last Update Posted (Actual)
September 27, 2022
Last Update Submitted That Met QC Criteria
September 9, 2022
Last Verified
September 1, 2022
More Information
Terms related to this study
Keywords
- endometrial cancer
- mesothelioma
- esophageal cancer
- ovarian cancer
- TNBC
- melanoma
- triple-negative breast cancer
- hepatocellular carcinoma (HCC)
- urothelial carcinoma
- squamous cell carcinoma of the head and neck
- renal cell carcinoma (RCC)
- SCCHN
- non-small cell lung cancer (NSCLC)
- Merkel cell carcinoma
- MSI-H CRC
- advanced or metastatic cervical cancer
- microsatellite instability-high colorectal cancer
- small cell lung cancer (SLCL)
- OX40 ligand (OX40)
- gastric cancer (including stomach and gastroesophageal junction [GEJ])
Additional Relevant MeSH Terms
Other Study ID Numbers
- INCAGN 1949-201
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Malignancies
-
Amsterdam UMC, location VUmcCompletedColorectum Advanced Malignancies | Breast Advanced Malignancies | Prostate Advanced MalignanciesNetherlands
-
AHS Cancer Control AlbertaCross Cancer InstituteWithdrawnMetastatic Solid Malignancies | Locally Advanced Solid MalignanciesCanada
-
Shandong TheraWisdom Biopharma Co., Ltd.RecruitingAdvanced MalignanciesChina
-
Innovent Biologics (Suzhou) Co. Ltd.Recruiting
-
AstraZenecaParexelCompletedAdvanced MalignanciesUnited Kingdom, United States
-
Innovent Biologics (Suzhou) Co. Ltd.Withdrawn
-
Millennium Pharmaceuticals, Inc.Completed
-
MedImmune LLCCompletedAdvanced MalignanciesUnited States
-
Bristol-Myers SquibbCompletedAdvanced MalignanciesUnited States
-
Symphony Evolution, Inc.Completed
Clinical Trials on INCAGN01949
-
Incyte Biosciences International SàrlCompletedMetastatic Cancer | Advanced MalignanciesUnited States, United Kingdom, Spain, Switzerland
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedStage IV Pancreatic Cancer AJCC v8 | Metastatic Pancreatic Adenocarcinoma | Locally Advanced Malignant Solid Neoplasm | Unresectable Malignant Solid NeoplasmUnited States