Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Melanoma

Stomach Neoplasms

Head and Neck Neoplasms

Carcinoma, Renal Cell

Lung Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Lymphoma

Urinary Bladder Neoplasms

Microsatellite Instability

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Skin Diseases

Adenocarcinoma

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Urologic Neoplasms

Urologic Diseases

Male Urogenital Diseases

Kidney Neoplasms

Kidney Diseases

Uterine Neoplasms

Uterine Diseases

Breast Diseases

Genomic Instability

Ovarian Cancer

Renal Cell Carcinoma

Stomach Cancer

Ovarian Epithelial Cancer

Lymphosarcoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Phase 1: MK-3475 + INCB024360 25 mg twice a day (BID) as starting dose, followed by dose escalations (Phase 1) until recommended phase 2 dose of INCB024360 is determined

MK-3475

INCB024360

Mark Jones, MD

The purpose of this study was to assess the safety, tolerability, and efficacy when combining MK-3475 and INCB024360 in participants with certain cancers. This study was conducted in 2 phases, Phase 1 and Phase 2.

Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers

A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of MK-3475 in Combination With INCB024360 in Subjects With Selected Cancers (ECHO-202/KEYNOTE-037)

An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful (i.e. defined as an event that jeopardizes the participant or requires potential medical or surgical intervention to prevent 1 of the outcomes listed above) or requires inpatient hospitalization or prolongation of existing hospitalization.

ORR was percentage of participants with best overall response \[complete response (CR) or partial response (PR)\], per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Duration of response is the time from the first overall response contributing to an objective response (complete or partial response) for DLBCL to the date of death or the date of first overall response of progressive diseasemeasured (by irRECIST for solid tumors or the Lugano Classification, whichever is earliest.

Progression-free survival is defined as number of days from the first day of taking study drug to the earlier of death or disease progression by irRECIST v1.1 for select solid tumors and modified Lugano Classification for DLBCL.

The duration of disease control is the time from the treatment start date to the first objective response of PD (by irRECIST v1.1 or Lugano Classification), death, or last tumor assessment date (if PD/death not present), for subjects with best overall response of SD or better.

Overall survival is determined from the date of first dose until death due to any cause.

Ordinal categorical response score, determined by radiographic disease assessments per irRECIST v1.1. The 5-category ordinal response endpoint is determined at a given timepoint by classifying response into one of the following groups: 1 = Complete response per irRECIST v1.1 2 = Very good response, defined as \> 60% tumor reduction 3 = Minor response, defined as \> 30% to ≤ 60% tumor reduction 4 = Stable disease per irRECIST v1.1 5 = Progressive disease per irRECIST v1.1

Merck Sharp & Dohme LLC

Incyte Corporation

The safety evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab).

Epacadostat 25 mg tablet orally twice daily (BID) starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1.

Phase 1: Epacadostat 25 mg BID

Epacadostat 50 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1.

Phase 1: Epacadostat 50 MG BID

Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1

Phase 1: Epacadostat 100 MG BID

Epacadostat 300 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1

Phase 1: Epacadostat 300 MG BID

Epacadostat 100 mg tablet orally BID in combination with pembrolizumab 200 mg intravenously every 3 weeks (Q3W).

Phase 2: Epacadostat 100 MG BID

Total

Phase 1: Epacadostat 50 mg BID

Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 2 mg/kg or 200mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1.

Phase 1: Epacadostat 100 mg BID

Epacadostat 300 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1.

Phase 1: Epacadostat 300 mg BID

Phase 2: Epacadostat 100 mg BID

Age, Continuous

Sex: Female, Male

White/Caucasian

Black/African-American

Asian

Native Hawaiian/Pacific Islander

Other

Missing

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Unknown

Study enrollment was permanently discontinued on 17 May 2018 as a strategic decision.

Study Director

TEAS

Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events

Triple negative breast cancer

Microsatellite-instability high colorectal cancer

Gastric cancer

Hepatocellular carcinoma

Melanoma - immune checkpoint-naïve

Non-small cell lung cancer (NSCLC) (tumor proportion score (TPS) < 50% or indeterminate)

NSCLC programmed cell death ligand (PD-L1) low negative (TPS < 50%)

Ovarian cancer

Renal cell carcinoma

Squamous cell carcinoma of the head and neck

Transitional carcinoma of the genitourinary (GU) tract

Diffuse large B-cell lymphoma

Primary Refractory Melanoma

Relapsed Melanoma

Epacadostat 100 mg BID+ Pembrolizumab 200 mg Q3W

The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type.

Phase 2: Objective Response Rate (ORR)

Hepatocellular Carcinoma

Triple Negative Breast Cancer

Immune Checkpoint-naïve Melanoma

NSCLC high positive (PD-L1 TPS ≥ 50%)

NSCLC low/negative or indeterminate (PD-L1 TPS < 50% or indeterminate)

NSCLC (TPS 0%)

NSCLC Unknown

Squamous Cell Carcinoma of the Head and Neck

Transitional Cell Carcinoma of the GU Tract

Gastric Cancer

MSI high Colorectal Cancer

DLBCL

Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with pembrolizumab 200 mg administered intravenously every 3 weeks (Q3W) starting on Cycle 1 Day 1.

The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab).

Number analyzed indicated participants analyzed in the respective tumor type and those who responded.

Phase 2: Duration of Response (DOR)

NSCLC

The efficacy evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab).

Number analyzed indicated participants analyzed in the respective tumor type.

Phase 2: Progression Free Survival (PFS)

NSCLC Total

The Efficacy Evaluable Population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type. The median time and the 90% CI were estimated using Kaplan-Meier method.

Phase 2: Duration of Disease Control

The Efficacy Evaluable Population included all participants enrolled in the study who received at least 1 dose of study drug. Number analyzed indicated participants analyzed in the respective tumor type. The median time and the 90% CI were estimated using Kaplan-Meier method.

Phase 2: Overall Survival (OS)

The Efficacy Evaluable Population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Number analyzed indicated participants analyzed in the respective tumor type.

Phase 2: Ordinal Categorical Response Score

Treatment-Emergent Adverse Events (TEAE)

Serious Treatment-Emergent Adverse Events

The safety evaluable population included all participants enrolled in the study who received at least 1 dose of study drug (epacadostat or pembrolizumab). Treatment groups for this population were determined according to the actual treatment the participant receives on Day 1. All safety analyses were conducted using the safety evaluable population.

Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events

Overall Study

Pancreatic Neoplasms

Pancreatic Cancer

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.

INCB050465

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

Carcinoma, Transitional Cell

Death

Transitional Cell Carcinoma

Cisplatin

Pembrolizumab administered intravenously every 3 weeks.

Epacadostat administered orally twice daily.

Epacadostat

Matching placebo administered orally twice daily.

Placebo

The purpose of this study was to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo in participants with cisplatin-ineligible urothelial carcinoma.

The study will be unblinded after the last participant completes Week 9 imaging assessment for efficacy analysis and after appropriate EC/IRB approvals have been received.

Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)

A Phase 3 Randomized, Double-Blind Trial of Pembrolizumab (MK-3475) in Combination With Epacadostat (INCB024360) or Placebo in Participants With Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)

ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination. Responses are based on Investigator assessments per RECIST 1.1 without confirmation using all scans up to the cutoff date.

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.

The All Participants as Treated (APaT) population was used for the safety analysis and consisted of all randomized participants who received at least 1 dose of study treatment. All-Cause Mortality was based on the ITT population and consisted of all randomized participants. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to the drug are excluded.

Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.

Pembrolizumab 200 mg + Epacadostat 100 mg BID

Pembrolizumab administered intravenously every 3 weeks. Matching placebo administered orally twice daily.

Pembrolizumab 200 mg + Placebo BID

Ethnicity (NIH/OMB)

White

Metastatic

Advanced/Unresectable

Metastasis Status at Screening

The Intention-to-Treat (ITT) population consisted of all randomized participants.

Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo

All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.

Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)

Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers	NCT02178722	Microsatellite-... Endometrial Can... Head and Neck C... Hepatocellular ... Gastric Cancer Lung Cancer Lymphoma Renal Cell Carc... Ovarian Cancer Solid Tumors UC (Urothelial ... Melanoma Bladder Cancer Triple Negative...	MK-3475 INCB024360	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
Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers	NCT02178722	Microsatellite-... Endometrial Can... Head and Neck C... Hepatocellular ... Gastric Cancer Lung Cancer Lymphoma Renal Cell Carc... Ovarian Cancer Solid Tumors UC (Urothelial ... Melanoma Bladder Cancer Triple Negative...	MK-3475 INCB024360	18 Years -	Incyte Corporation
Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)	NCT03361865	UC (Urothelial ...	Pembrolizumab Epacadostat Placebo	18 Years -	Incyte Corporation
A Study of Atezolizumab (MPDL3280A) in Combination With Epacadostat (INCB024360) in Subjects With Previously Treated Stage IIIB or Stage IV Non-Small Cell Lung Cancer and Previously Treated Stage IV Urothelial Carcinoma (ECHO-110)	NCT02298153	NSCLC (Non-smal... UC (Urothelial ...	atezolizumab epacadostat	18 Years -	Incyte Corporation
Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma	NCT03374488	UC (Urothelial ...	Pembrolizumab Epacadostat Placebo	18 Years -	Incyte Corporation
A Study of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)	NCT02318277	Solid Tumors Head and Neck C... Lung Cancer UC (Urothelial ...	MEDI4736 INCB024360	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for uc (urothelial cancer)