Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Renal Cell

Neoplasm Metastasis

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplastic Processes

Ovarian Cancer

Renal Cell Carcinoma

Ovarian Epithelial Cancer

Clear Cell Renal Cell Carcinoma

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Initial cohort dose of INCAGN01949 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.

INCAGN01949

John E. Janik, MD

The purpose of this study is to determine the safety and tolerability and assess preliminary efficacy of INCAGN01949 in subjects with advanced or metastatic solid tumors.

A Phase 1/2, Open-Label, Dose-Escalation, Safety Study of INCAGN01949 in Subjects With Advanced or Metastatic Solid Tumors

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN01949 in Subjects With Advanced or Metastatic Solid Tumors

Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment

To evaluate the Cmax of INCAGN01949 in subjects with advanced or metastatic solid tumors.

To evaluate the AUC0-t of INCAGN01949 in subjects with advanced or metastatic solid tumors

ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 and mRECIST v1.1. by investigator determination.

To evaluate the Tmax of INCAGN01949 in subjects with advanced or metastatic solid tumors.

To evaluate the Cmin of INCAGN01949 in subjects with advanced or metastatic solid tumors. Cmin is the minimum observed concentration of INCAGN1949

Incyte Biosciences International Sàrl

INCAGN01949 7mg administered intravenously over a 30-minute period on Day 1 of each cycle in subjects with advanced or metastatic solid tumors

PART 1 Dose 1 (7 mg)

INCAGN01949 20mg administered intravenously over a 30-minute period on Day 1 of each cycle in subjects with advanced or metastatic solid tumors

PART 1 Dose 2 (20 mg)

INCAGN01949 70mg administered intravenously over a 30-minute period on Day 1 of each cycle in subjects with advanced or metastatic solid tumors

PART 1 Dose 3 (70 mg)

INCAGN01949 200mg administered intravenously over a 30-minute period on Day 1 of each cycle in subjects with advanced or metastatic solid tumors

PART 1 Dose 4 (200 mg)

INCAGN01949 350mg administered intravenously over a 30-minute period on Day 1 of each cycle in subjects with advanced or metastatic solid tumors

PART 1 Dose 5 (350 mg)

INCAGN01949 700mg administered intravenously over a 30-minute period on Day 1 of each cycle in subjects with advanced or metastatic solid tumors

PART 1 Dose 6 (700 mg)

INCAGN01949 1400mg administered intravenously over a 30-minute period on Day 1 of each cycle in subjects with advanced or metastatic solid tumors

PART 1 Dose 7 (1400 mg)

Total

Age, Continuous

Sex: Female, Male

White/Caucasian

Asian

Other

Black/African American

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Not Reported

The PK evaluable population will include all subjects who received at least 1 dose of INCAGN01949 and provided at least 1 post dose sample (1 PK measurement).

Maximum Observed Concentration (Cmax) of INCAGN01949 in Plasma

cycle 1

cycle 6

Area Under the Single-dose Concentration-time Curve (AUC0-t) of INCAGN01949

The Full Analysis Set population include all subjects enrolled in the study who received at least 1 dose of INCAGN01949.

Objective Response Rate Per RECIST and Modified RECIST

The Full Analysis Set population included all subjects enrolled in the study who received at least 1 dose of INCAGN01949. Median was not estimable due to insufficient number of participants with response

Duration of Response Per RECIST and Modified RECIST

Progression-free Survival Per RECIST and Modified RECIST

The Full Analysis Set population include all subjects enrolled in the study who received at least 1 dose of INCAGN01949. Median was not estimable due to insufficient number of participants with CR, PR, and SD

Duration of Disease Control Per RECIST and Modified RECIST

Number of Participants With Treatment-related Adverse Events

Time to Maximum Concentration of INCAGN01949 in Plasma

cycle 2

cycle 3

cycle 4

cycle 7

Summary of Trough Concentrations(Cmin) of INCAGN01949

Overall Study

Digestive System Diseases

Infections

Carcinoma, Squamous Cell

Stomach Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Esophageal Neoplasms

Carcinoma, Hepatocellular

Uterine Cervical Neoplasms

Small Cell Lung Carcinoma

Microsatellite Instability

Carcinoma, Transitional Cell

Squamous Cell Carcinoma of Head and Neck

Mesothelioma

Mesothelioma, Malignant

Carcinoma, Merkel Cell

Stomach Cancer

Esophageal Cancer

Small Cell Lung Cancer

Transitional Cell Carcinoma

Malignant Mesothelioma

Merkel Cell Carcinoma

Antineoplastic Agents

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

INCAGN01949 (70, 200, 350, or 700 milligrams \[mg\]) combined with nivolumab 240 mg in participants with advanced or metastatic select solid tumors

INCAGN01949 (70, 200, 350, or 700 mg) combined with ipilimumab 1 mg/kilogram (kg) in participants with advanced or metastatic select solid tumors

INCAGN01949 combined with nivolumab 3 mg/kg and ipilimumab 1 mg/kg in participants with advanced or metastatic select solid tumors

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

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

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)

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Treatment-emergent adverse events, defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug, have been reported.

Participants with advanced or metastatic select solid tumors received INCAGN01949 70 milligrams (mg) every 2 weeks (Q2W) beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 1 Day 1, administered as intravenous (IV) infusions.

Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg

Participants with advanced or metastatic select solid tumors received INCAGN01949 200 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 1 Day 1, administered as IV infusions.

Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg

Participants with advanced or metastatic select solid tumors received INCAGN01949 350 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 1 Day 1, administered as IV infusions.

Phase 1, Dose Escalation: INCAGN01949 350 mg + Nivolumab 240 mg

Participants with advanced or metastatic select solid tumors received INCAGN01949 700 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 1 Day 1, administered as IV infusions.

Phase 1, Dose Escalation: INCAGN01949 700 mg + Nivolumab 240 mg

Participants with advanced or metastatic select solid tumors received INCAGN01949 70 mg Q2W beginning on Cycle 1 Day 1, followed by ipilimumab 1 mg/kilogram (kg) every 6 weeks (Q6W) beginning on Cycle 1 Day 1, administered as IV infusions.

Phase 1, Dose Escalation: INCAGN01949 70 mg + Ipilimumab 1 mg/kg

Participants with advanced or metastatic select solid tumors received INCAGN01949 200 mg Q2W beginning on Cycle 1 Day 1, followed by ipilimumab 1 mg/kg Q6W beginning on Cycle 1 Day 1, administered as IV infusions.

Phase 1, Dose Escalation: INCAGN01949 200 mg + Ipilimumab 1 mg/kg

Participants with advanced or metastatic select solid tumors received INCAGN01949 350 mg Q2W beginning on Cycle 1 Day 1, followed by ipilimumab 1 mg/kg Q6W beginning on Cycle 1 Day 1, administered as IV infusions.

Phase 1, Dose Escalation: INCAGN01949 350 mg + Ipilimumab 1 mg/kg

Participants with advanced or metastatic select solid tumors received INCAGN01949 700 mg Q2W beginning on Cycle 1 Day 1, followed by ipilimumab 1 mg/kg Q6W beginning on Cycle 1 Day 1, administered as IV infusions.

Phase 1, Dose Escalation: INCAGN01949 700 mg + Ipilimumab 1 mg/kg

Participants with advanced or metastatic select solid tumors received INCAGN01949 70 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 3 Day 1, administered as IV infusions.

Phase 1, Safety Expansion: INCAGN01949 70 mg + Nivolumab 240 mg

Participants with advanced or metastatic select solid tumors received INCAGN01949 200 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 3 Day 1, administered as IV infusions.

Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg

Participants with advanced or metastatic select solid tumors received INCAGN01949 350 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 3 Day 1, administered as IV infusions.

Phase 1, Safety Expansion: INCAGN01949 350 mg + Nivolumab 240 mg

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Because there was limited clinical efficacy, with 3 confirmed responders, Phase 2 of the study did not open for enrollment. There were no safety concerns.

Study Director

Full Analysis Set (FAS): all participants enrolled in the study who received ≥ 1 dose of INCAGN01949, nivolumab, or ipilimumab

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

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

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) were to have received a range of doses of INCAGN01949 found to be safe in Phase 1 in combination with nivolumab, administered as IV infusions

Phase 2, Part A: INCAGN01949 + Nivolumab

PD-1/L1 refractory participants with advanced or metastatic gastric cancer, SCCHN, NSCLC, or RCC were to have received a range of doses of INCAGN01949 found to be safe in Phase 1. INCAGN01949 was to have been administered alone, in combination with nivolumab, and in combination with nivolumab and ipilimumab, administered as IV infusions.

Phase 2, Part B: INCAGN01949; INCAGN01949 + Nivolumab; INCAGN01949 + Nivolumab + Ipilimumab

Phase 2 of the study did not open for enrollment.

Phase 2: Objective Response Rate (ORR)

Phase 1: ORR

FAS. The confidence interval was calculated using the method of Brookmeyer and Crowley. Only participants with a confirmed CR or PR were analyzed.

Phase 1: Duration of Response (DOR)

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) were to have received a range of doses of INCAGN01949 found to be safe in Phase 1 in combination with nivolumab, administered as IV infusions.

Phase 2: DOR

Phase 1: Disease Control Rate (DCR)

Phase 2: DCR

FAS. The confidence interval was calculated based on the exact method for binomial distributions. Only participants with a confirmed CR, PR, or SD were analyzed.

Phase 1: Duration of Disease Control

Phase 2: Duration of Disease Control

FAS. Median survival time was estimated using the Kaplan-Meier method. The confidence interval was calculated using the method of Brookmeyer and Crowley. Only participants with events of disease progression or death were analyzed.

Phase 1: Progression-free Survival (PFS)

Phase 2: PFS

Phase 2: Number of Participants With TEAEs

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

Participants with advanced or metastatic select solid tumors were to have received INCAGN01949 at the assigned dose level Q2W in combination with nivolumab 3 mg/kg Q2W and ipilimumab 1 mg/kg Q6W, all administered as IV infusions beginning on Cycle 1 Day 1.

Phase 1, Dose Escalation: INCAGN01949 + Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg

Participants with advanced or metastatic solid tumors were to have received INCAGN01949 at the assigned dose level Q2W beginning on Cycle 1 Day 1, in combination with nivolumab 3 mg/kg Q2W beginning on Cycle 3 Day 1 and ipilimumab 1 mg/kg Q6W beginning on Cycle 3 Day 1, administered as IV infusions.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1/2, Open-Label, Dose-Escalation, Safety Study of INCAGN01949 in Subjects With Advanced or Metastatic Solid Tumors	NCT02923349	Advanced Malign... Metastatic Canc...	INCAGN01949	18 Years -	Incyte Corporation
A Phase 1/2, Open-Label, Dose-Escalation, Safety Study of INCAGN01949 in Subjects With Advanced or Metastatic Solid Tumors	NCT02923349	Advanced Malign... Metastatic Canc...	INCAGN01949	18 Years -	Incyte Corporation
A Study Exploring the Safety and Efficacy of INCAGN01949 in Combination With Immune Therapies in Advanced or Metastatic Malignancies	NCT03241173	Advanced Malign...	INCAGN01949 Nivolumab Ipilimumab	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for incagn01949

Every month we try and update this database with for incagn01949 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for incagn01949

Every month we try and update this database with for incagn01949 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for incagn01949 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.