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

Advanced Malignancies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03241173
• Other study ID #: INCAGN 1949-201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 9, 2017
• Est. completion date: September 17, 2019

Study information

• Verified date: September 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: September 17, 2019
• Est. primary completion date: September 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Malignancies
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	The University of Alabama Birmingham (UAB)	Birmingham	Alabama
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	John Theurer Cancer Center At Hackensack UMC	Hackensack	New Jersey
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	Mount Sinai Medical Center of Florida, Inc.	Miami	Florida
United States	Sarah Cannon Research Institute, LLC (SCRI)	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers, The State University	New Brunswick	New Jersey
United States	New York University Clinical Cancer Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	Scottsdale Healthcare Hospitals DBA HonorHealth	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Biosciences International Sàrl

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 17.4 months
Primary	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.	up to 17.4 months
Primary	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.	up to 24 months
Secondary	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.	up to 15.6 months
Secondary	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.	up to 11.0 months
Secondary	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.	up to 24 months
Secondary	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.	up to 15.6 months
Secondary	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.	up to 24 months
Secondary	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.	up to 15.4 months
Secondary	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.	up to 24 months
Secondary	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.	up to 15.6 months
Secondary	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.	up to 24 months
Secondary	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.	up to 24 months
Secondary	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.	up to 24 months