Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Adenocarcinoma

Neoplasm Metastasis

Necrosis

Melanoma

Carcinoma, Renal Cell

Neoplastic Processes

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

All Drugs and Chemicals

Glucocorticoids

Participants received IV infusion of study drug at a dose of 20.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Participants received intravenous (IV) infusion of study drug at a dose of 0.03 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Participants received IV infusion of study drug at a dose of 0.1 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Participants received IV infusion of study drug at a dose of 0.3 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Participants received IV infusion of study drug at a dose of 1.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Participants received IV infusion of study drug at a dose of 3.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Participants received IV infusion of study drug at a dose of 5.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Participants received IV infusion of study drug at a dose of 10.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Participants received IV infusion of study drug at a dose of 400 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Participants received IV infusion of study drug at a dose of 300 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months.

Initial cohort dose of INCAGN01876 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.

INCAGN01876

John Janik, MD

This was an open-label, non-randomized Phase 1/2 safety study of INCAGN01876 in participants with advanced or metastatic solid tumors that was conducted in 2 parts. Part 1 is dose escalation and safety expansion which determines the optimal dose and maximum number of tolerated doses. Part 2 is dose expansion in which Part 1 recommended dose will be evaluated.

A Study of INCAGN01876 in Participants With Advanced or Metastatic Solid Tumors

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN01876 in Subjects With Advanced or Metastatic Solid Tumors

AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent AE is any AE either reported for first time or worsening of a pre-existing event after the first dose of study drug. Grade 1 AEs is defined as Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 AEs is defined as Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3 AEs is defined as the severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living and Grade 4 AEs as life-threatening consequences; urgent intervention indicated. Data is reported for Grade 3 and higher severity for this outcome measure.

ORR is defined as the percentage of participants having complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease assessments. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.

DOR is defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.

Duration of disease control (CR, PR, and stable disease \[SD\]), as measured from first report of SD or better until disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

PFS is defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. Progression is defined by RECIST and mRECIST as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute lesion increase of at least 5 mm or the appearance of new lesions.

Incyte Biosciences International Sàrl

Participants received IV infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months.

Phase 1: 0.03 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 0.1 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months.

Phase 1: 0.1 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 0.3 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months.

Phase 1: 0.3 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 1.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months.

Phase 1: 1.0 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 3.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months.

Phase 1: 3.0 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 5.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months.

Phase 1: 5.0 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 10.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months.

Phase 1: 10.0 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 20.0 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months.

Phase 1: 20.0 mg/kg Q2W

Participants received IV infusion of study drug at a dose of 400 mg Q4W starting on Day 1 of each cycle for up to 15 months.

Phase 1: 400 mg Q4W

Participants received IV infusion of study drug at a dose of 300 mg Q2W starting on Day 1 of each cycle for up to 15 months.

Phase 2: 300 mg Q2W

Total

INCAGN01876 was administered at 0.03mg/kg Q2W as part of dose escalation.

INCAGN01876 was administered at 0.1mg/kg Q2W as part of dose escalation.

INCAGN01876 was administered at 0.3mg/kg Q2W as part of dose escalation.

INCAGN01876 was administered at 1.0mg/kg Q2W as part of dose escalation.

INCAGN01876 was administered at 3mg/kg Q2W as part of dose escalation.

INCAGN01876 was administered at 5mg/kg Q2W as part of dose escalation.

INCAGN01876 was administered at 10mg/kg Q2W as part of dose escalation.

INCAGN01876 was administered at 20mg/kg Q2W as part of dose escalation.

INCAGN01876 was administered at 400mg Q4W as part of dose escalation.

INCAGN01876 was administered at 300mg Q2W as part of dose escalation.

Age, Continuous

Sex: Female, Male

Ethnicity

Race/Ethnicity, Customized

Race

ECOG performance status is used to assess how a participant's disease is progressing and assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. Graded from 0-5 where 0=Fully Active (Most Favorable Activity); 1=Restricted activity but ambulatory; 2=Ambulatory but unable to carry out work activities; 3=Limited Self-Care; 4=Completely Disabled, No self-care; 5=Dead (Least Favorable Activity).

ECOG Performance Status

The full analysis set (FAS) included all participants enrolled in the study who received at least 1 dose of study drug.

Study Director

TEAEs

Grade 3 and Higher

Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity

Cycle 1 (After the First Dose)

Cycle 6

The pharmacokinetic (PK) evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement).

Maximum Observed Plasma Concentration (Cmax)

The PK evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement).

Time to Maximum Concentration (Tmax)

Cycle 2

Cycle 3

Cycle 4

Cycle 7

The PK evaluable population included all participants who received at least 1 dose of study drug and provided at least 1 post dose sample (1 PK measurement). Data is presented for those cycles for which data is available.

Minimum Observed Plasma Concentration Over the Dose Interval (Cmin)

Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t)

RECIST v1.1

mRECIST v1.1

The FAS included all participants enrolled in the study who received at least 1 dose of study drug.

Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST)

Duration of Response (DOR) Per RECIST and mRECIST

Duration of Disease Control Per RECIST and mRECIST

PFS under RECIST v1.1

PFS under mRECIST v1.1

Progression Free Survival (PFS) Per RECIST and mRECIST

Participants received intravenous (IV) infusion of study drug at a dose of 0.03 mg/kg Q2W starting on Day 1 of each cycle for up to 15 months.

Overall Study

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

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

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)

White/Caucasian

Asian

Other

Black/African American

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of INCAGN01876 in Participants With Advanced or Metastatic Solid Tumors	NCT02697591	Advanced Malign... Metastatic Canc...	INCAGN01876	18 Years -	Incyte Corporation
A Study of INCAGN01876 in Participants With Advanced or Metastatic Solid Tumors	NCT02697591	Advanced Malign... Metastatic Canc...	INCAGN01876	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 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

Spots Global Cancer Trial Database for adenocarcinoma of the endometrium