Part 1: INCMGA00012 at the protocol-defined starting dose administered intravenously every 4 weeks, with dose escalation to determine the maximum tolerated dose.

Part 2: INCMGA00012 at the recommended dose from Part 1.

Retifanlimab

Part 1: Epacadostat at the protocol-defined starting dose administered orally twice daily, with dose escalation to determine the maximum tolerated dose.

Part 2: Epacadostat at the recommended dose from Part 1.

Epacadostat

Part 1: INCB050465 at the protocol-defined starting dose administered orally once daily, with dose escalation to determine the maximum tolerated dose. Part 2: INCB050465 at the recommended dose from Part 1.

INCB050465

The purpose of this study is to determine the safety, preliminary evidence of clinical activity, and recommended Phase 2 dose (RP2D) of INCMGA00012 in combination with other agents that may improve the therapeutic efficacy of anti-PD-1 monotherapy.

INCMGA00012 in Combination With Other Therapies in Patients With Advanced Solid Tumors

A Phase 1b Study of INCMGA00012 in Combination With Other Therapies in Patients With Advanced Solid Tumors

Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.

Defined as maximum observed plasma or serum concentration. Other pharmacokinetic measures (including Cmin and AUC0-t) will also be evaluated.

Defined as time to maximum concentration. Other pharmacokinetic measures (including Cmin and AUC0-t) will also be evaluated.

Defined as the percentage of participants having complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST v1.1 for immune-based therapeutics.

Defined as the time from the earliest date of CR or PR until the earliest date at which progression criteria are met or date of death due to any cause, whichever occurs first.

Defined as the time from the start of therapy until the earliest date at which progression criteria are met or date of death due to any cause, whichever occurs first.

Defined as the time from randomization to death due to any cause.

Incyte Corporation

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

INCB053914 in combination with INCB050465.

Dose Escalation: INCB053914 at the protocol-defined starting dose in combination with INCB050465, with dose modifications based on tolerability criteria.

Dose Expansion: Recommended dose from the dose-escalation study.

INCB053914

Dose Escalation: INCB050465 at the protocol-defined starting dose in combination with INCB053914, with dose modifications based on tolerability criteria.

Dose Expansion: Recommended dose from the dose-escalation study.

Fred Zheng, MD

The purpose of this study is to evaluate the safety and tolerability of INCB053914 in combination with INCB050465 in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

A Safety and Tolerability Study of INCB053914 in Combination With INCB050465 in Diffuse Large B-Cell Lymphoma

A Phase 1b, Multicenter, Open-Label Study of the Safety and Tolerability of INCB053914 in Combination With INCB050465 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

TEAE is defined as an adverse event reported for the first time or worsening of a pre-existing event after the first dose of study treatment.

Minimum observed plasma concentration during the dosing interval.

Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration.

Defined as the percentage of participants with a complete remission (CR)/complete metabolic response (CMR) or partial remission (PR)/partial metabolic response (PMR) as defined by investigator assessment per revised Lugano classification criteria for lymphomas.

Defined as the time from first documented evidence of CR/CMR or PR/PMR until disease progression or death from any cause among participants who achieve an objective response, as determined by radiographic disease assessment.

Defined as the time from the date of the first dose of any study drug until the earliest date of disease progression, as determined by radiographic disease assessment, or death from any cause, whichever occurs first.

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Lung Neoplasms

Carcinoma

Breast Neoplasms

Pancreatic Neoplasms

Melanoma

Carcinoma, Renal Cell

Head and Neck Neoplasms

Endometrial Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Pancreatic Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Part 1a Group A will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days.

Part 1b Group A-1 and Group A-2 will evaluate the MTD or PAD of itacitinib in combination with pembrolizumab in subjects with select solid tumors.

Part 1a Group B will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days.

Part 1b Group B-1 and Group B-2 will evaluate the MTD or PAD of INCB050465 in combination with pembrolizumab in subjects with select solid tumors.

Part 2 will evaluate the combination of INCB050465 in combination with pembrolizumab in subjects with small cell lung cancer, non-small lung cancer and urothelial cancer.

Itacitinib tablets administered orally once daily.

itacitinib

INCB050465 tablets administered orally once daily.

Peter B. Langmuir, MD

This is an open-label, multicenter, Phase 1b platform study in subjects with advanced or metastatic solid tumors (Part 1a) and subjects with selected solid tumors (Part 1b and Part 2). Two treatment groups (Group A and Group B) will be evaluated

Part 1a utilizes a 3+3 design to evaluate pembrolizumab and INCB combinations in advanced solid tumors. Group A will evaluate a JAK inhibitor with JAK1 selectivity itacitinib (INCB039110) in combination with pembrolizumab (MK-3475) and Group B will evaluate a PI3K-delta inhibitor (INCB050465) in combination with pembrolizumab to determine the maximum tolerated dose (MTD) or PAD and recommend a dose for the Part 1b safety expansion with each combination.

Once the recommended dose has been identified in Part 1a, subjects with select solid tumor types will be enrolled into safety expansion cohorts based upon prior treatment history with a PD-1 pathway-targeted agent (Part 1b) for each combination.

Part 2 utilizes a Simon 2-Stage design to evaluate INCB050465 in combination with pembrolizumab in patients with small cell lung cancer (SCLC) and a 1 stage design to evaluate the combination in patients with non-small cell lung cancer (NSCLC) and urothelial cancer (UC).

This is an open-label, Phase 1b, 3 Part (Part 1a, Part 1b, and Part 2), multi-center study.

Part 1a utilizes a 3+3 design to evaluate pembrolizumab and INCB combinations in advanced solid tumors. Group A will evaluate a JAK inhibitor with JAK1 selectivity itacitinib (INCB039110) in combination with pembrolizumab (MK-3475) and Group B will evaluate a PI3K-delta inhibitor (INCB050465) in combination with pembrolizumab to determine the maximum tolerated dose (MTD) or PAD and recommend a dose for the Part 1b safety expansion with each combination.

Once the recommended dose has been identified in Part 1a, subjects with endometrial cancer, gastric cancer, melanoma, microsatellite unstable (MSI) colorectal cancer or other MMR-deficient tumors, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, triple negative breast cancer, pancreatic ductal carcinoma, or transitional cell carcinoma of the genitourinary tract will be enrolled into safety expansion cohorts based upon prior treatment history with a PD-1 pathway-targeted agent (Part 1b) for each combination.

Part 2 utilizes a Simon 2-Stage design to evaluate INCB050465 in combination with pembrolizumab in patients with small cell lung cancer (SCLC) and a 1 stage design to evaluate the combination in patients with non-small cell lung cancer (NSCLC) and urothelial cancer (UC).

Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors

A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of Pembrolizumab + INCB Combinations in Advanced Solid Tumors

Symptoms and General Pathology

Neoplasm Metastasis

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Gemcitabine

Paclitaxel

Dexamethasone

Azacitidine

Albumin-Bound Paclitaxel

Lenalidomide

Bortezomib

Pomalidomide

Dexamethasone acetate

Janus Kinase Inhibitors

Tubulin Modulators

Antimitotic Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antimetabolites

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Enzyme Inhibitors

Initial cohort dose of INCB052793 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria.

INCB052793

Gemcitabine administered intravenously over 30 minutes at the protocol-specified dose and frequency.

gemcitabine

nab-paclitaxel administered intravenously over 30 minutes at the protocol-specified dose and frequency.

nab-paclitaxel

Dexamethasone administered orally at the protocol-specified dose and frequency.

dexamethasone

Carfilzomib administered intravenously at the protocol-specified dose and frequency.

Carfilzomib

Bortezomib administered intravenously or subcutaneously at the protocol-specified dose and frequency.

bortezomib

Lenalidomide administered orally at the protocol-specified dose and frequency.

lenalidomide

Azacitidine administered subcutaneously at the protocol-specified dose and frequency.

azacitidine

INCB052793 tablets administered orally at the protocol specified dose strength and frequency.

Pomalidomide administered orally at the protocol-specified dose and frequency.

pomalidomide

INCB050465 tablets administered orally at the protocol specified dose strength and frequency.

INCB039110 tablets administered orally at the protocol specified dose strength and frequency.

INCB039110

Ekaterine Asatiani, M.D.

This was a study of INCB052793 given to patients with advanced malignancies that was to be conducted in three phases; Phase 1a (Monotherapy) and Phase 1b (Combination Therapy) and Phase 2 (Combination therapy of INCB052793 with azacitidine and itacitinib with azacitidine). Phase 1 had two parts; a dose escalation (Part 1) and an expansion (Part 2).

An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB052793 in Subjects With Advanced Malignancies

An AE is any untoward medical occurrence in a subject administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. A TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last dose of study drug.

ORR is defined as the proportion of participants who achieved complete response (CR), CR with incomplete hematologic recovery (CRi), partial response (PR), or hematologic improvement (HI), using the IWG response criteria.

Response rate is defined as the percentage of participants who achieved best overall response (BOR) as determined by IWG response criteria of investigator's assessment. A participant was considered an objective responder based on the following- Solid tumors: participant had a best overall response (BOR) of CR or PR, Lymphoma: participant had a BOR of complete radiologic response/complete metabolic response or partial remission/partial metabolic response, AML: participant had a BOR of CR, CRi, morphological leukemia-free state (MLFS), or PR, MDS: participant had a BOR of CR, PR, or marrow CR, MDS/myeloproliferative neoplasm (MPN): participant had a BOR of CR, PR, or marrow response, MM: participant had a BOR of stringent CR, CR, very good PR, PR, or MR. Subjects are combined by tumor type for this analysis.

Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.

Tmax is the time to maximum (peak) observed plasma drug concentration. Summary of Steady-State, Day 15, was evaluated by dosing regimen. For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.

AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.

Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15).

Tmax is the time to maximum (peak) observed plasma drug concentration.

AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).

Cmax is defined as the maximum observed plasma concentration measured at Day 1.

AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.

Minimum observed plasma concentration measured at steady state (Day 15).

AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).

AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.

Cmax is defined as the maximum observed plasma concentration measured at cycle 2 Day 1.

Cmin is defined as the minimal observed plasma concentration measured at cycle 2 Day 1

INCB052793 15 mg tablet, orally (PO), once daily (QD) in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 78.3 days ).

Phase 1a TGA - INCB052793 15 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 96.3 days).

Phase 1a TGA - INCB052793 25 mg

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 80.3 days).

Phase 1a TGA - INCB052793 35 mg

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 46.5 days).

Phase 1a TGA - INCB052793 50 mg

INCB052793 75 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 459.0 days).

Phase 1a TGA - INCB052793 75 mg

INCB052793 100 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 44.0 days).

Phase 1a TGA - INCB052793 100 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 248.7 days).

Phase 1a TGB - INCB052793 25 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 342.8 days).

Phase 1a TGB - INCB052793 35 mg

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 76.3 days).

Phase 1a TGB - INCB052793 50 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with multiple myeloma (MM) in continuous 21 day cycles until they met treatment discontinuation criteria plus Dexamethasone 40 mg, PO, weekly for each 28-day cycle (Up to mean duration of exposure of approximately 53.6 days).

Phase 1b Cohort B - INCB052793 25 mg + Dexamethasone 40 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) in continuous 21 day cycles until they met treatment discontinuation criteria plus Azacitidine 75 mg/m\^2, subcutaneous (SC) injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 28-day cycle (Up to mean duration of exposure of approximately 151.2 days).

Phase 1b Cohort F - INCB052793 25 mg + Azacytidine 75 mg/m^2

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with AML/MDS in continuous 21 day cycles until they met treatment discontinuation criteria Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 28-day cycle (Up to mean duration of exposure of approximately 142.1 days).

Phase 1b Cohort F - INCB052793 35 mg + Azacytidine 75 mg/m^2

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with hypomethylating agent-refractory (HMA)-refractory AML and high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 28-day cycle (Up to mean duration of exposure of approximately 86.2 days).

Phase 2 Cohort I - INCB052793 35 mg + Azacytidine 75 mg/m^2

Itacitinib 300 mg sustained-release tablet, PO, QD in the fasted state in participants with HMA-refractory AML and high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 28-day cycle (Up to mean duration of exposure of approximately 143 days).

Phase 2 Cohort J - Itacitinib 300 mg + Azacitidine 75 mg/m^2

INCB052793 15 mg tablet, orally (PO), once daily (QD) in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 75 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 100 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with multiple myeloma (MM) in continuous 21 day cycles until they met treatment discontinuation criteria plus Dexamethasone 40 mg, PO, weekly for each 21-day cycle.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) in continuous 21 day cycles until they met treatment discontinuation criteria plus Azacitidine 75 mg/m\^2, subcutaneous (SC) injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle.

The safety evaluable population included all subjects enrolled in the study who receivedat least 1 dose of study treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
INCMGA00012 in Combination With Other Therapies in Patients With Advanced Solid Tumors	NCT03589651	Unresectable or...	Retifanlimab Epacadostat INCB050465	18 Years -	Incyte Corporation
A Safety and Tolerability Study of INCB053914 in Combination With INCB050465 in Diffuse Large B-Cell Lymphoma	NCT03688152	Relapsed Diffus... Refractory Diff...	INCB053914 INCB050465	18 Years -	Incyte Corporation
Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors	NCT02646748	Colorectal Canc... Endometrial Can... Melanoma Head and Neck C... Lung Cancer MMR-deficient T... Breast Cancer Pancreatic Canc... Renal Cell Carc... Solid Tumors UC (Urothelial ...	Pembrolizumab itacitinib INCB050465	18 Years -	Incyte Corporation
An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies	NCT02265510	Solid Tumors Advanced Malign... Metastatic Canc...	INCB052793 gemcitabine nab-paclitaxel dexamethasone Carfilzomib bortezomib lenalidomide azacitidine INCB052793 pomalidomide INCB050465 INCB039110	18 Years -	Incyte Corporation
Itacitinib Combined With INCB024360 and/or Itacitinib Combined With INCB050465 in Advanced Solid Tumors	NCT02559492	Solid Tumors	Itacitinib Epacadostat Itacitinib INCB050465	18 Years -	Incyte Corporation
Itacitinib Combined With INCB024360 and/or Itacitinib Combined With INCB050465 in Advanced Solid Tumors	NCT02559492	Solid Tumors	Itacitinib Epacadostat Itacitinib INCB050465	18 Years -	Incyte Corporation
To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis (LIMBER-313)	NCT04551066	Myelofibrosis Primary Myelofi... Post Essential ... Post Polycythem...	parsaclisib ruxolitinib placebo	18 Years -	Incyte Corporation
To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)	NCT04551053	Myelofibrosis Primary Myelofi... Post Essential ... Post Polycythem...	parsaclisib ruxolitinib placebo	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for incb050465

Every month we try and update this database with for incb050465 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 incb050465

Every month we try and update this database with for incb050465 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 incb050465 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.