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Study of Epacadostat (INCB024360) Alone and In Combination With Pembrolizumab (MK-3475) With Chemotherapy and Pembrolizumab Without Chemotherapy in Participants With Advanced Solid Tumors (MK-3475-434)

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ClinicalTrials.gov Identifier: NCT02862457
Recruitment Status : Completed
First Posted : August 11, 2016
Last Update Posted : February 2, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

This is an open-label, non-randomized, Phase I study of epacadostat (INCB024360) alone and in combination with pembrolizumab with chemotherapy and pembrolizumab without chemotherapy in participants with advanced solid tumors. The primary objective of the trial is to evaluate the safety and tolerability of epacadostat administered alone and in combination with pembrolizumab with and without chemotherapy.

With protocol amendment 02 (26-April-2019), treatment with epacadostat was stopped in the "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", and "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.


Condition or disease Intervention/treatment Phase
Neoplasms Carcinoma, Non-Small-Cell Lung Drug: Epacadostat 25 mg Drug: Epacadostat 100 mg Biological: pembrolizumab 200 mg Drug: Cisplatin 75 mg/m^2 Drug: Carboplatin Area Under the Curve (AUC)5 Drug: Pemetrexed 500 mg/m^2 Drug: Paclitaxel 200 mg/m^2 Drug: Carboplatin AUC6 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of INCB024360 (Epacadostat) Alone, INCB024360 in Combination With Pembrolizumab (MK-3475), and INCB024360 and Pembrolizumab in Combination With Chemotherapy in Patients With Advanced Solid Tumors (KEYNOTE-434)
Actual Study Start Date : August 23, 2016
Actual Primary Completion Date : November 20, 2020
Actual Study Completion Date : November 20, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Epacadostat (Epacad)
Cycle 1 is a dose escalation study in which participants will receive 25 or 100 mg of epacadostat orally twice daily (BID) alone on Days 1-5 of Cycle 1 with a washout on Days 6 and 7. On Day 8 of Cycle 1 participants will receive a one-time intravenous (IV) infusion of 200 mg pembrolizumab while continuing to receive 25 or 100 mg of epacadostat orally BID on Days 8-28. For Cycles 2 through 35 participants will receive a one-time IV infusion of 200 mg pembrolizumab on Day 1 and receive 25 or 100 mg of epacadostat orally BID on Days 1-21.
Drug: Epacadostat 25 mg
25 mg tablet administered orally, twice a day (BID) on Days 1-5 and Days 8-28 of Cycle 1 (28-day Cycle) and Days 1-21 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Days 1-21 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)" study arm.
Other Name: INCB024360

Drug: Epacadostat 100 mg
100 mg tablet administered orally, twice a day (BID) on Days 1-5 and Days 8-28 of Cycle 1 (28-day Cycle) and Days 1-21 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Days 1-21 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Name: INCB024360

Biological: pembrolizumab 200 mg
Administered as an intravenous (IV) infusion on Day 8 of Cycle 1 (28 days) and Day 1 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Day 1 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Epacad+Pembrolizumab (Pembro)
For each 21-day cycle, participants will receive a one-time IV infusion of 200 mg pembrolizumab on Day 1 and receive 25 or 100 mg of epacadostat orally BID on Days 1-21 for a maximum of 35 cycles.
Drug: Epacadostat 25 mg
25 mg tablet administered orally, twice a day (BID) on Days 1-5 and Days 8-28 of Cycle 1 (28-day Cycle) and Days 1-21 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Days 1-21 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)" study arm.
Other Name: INCB024360

Drug: Epacadostat 100 mg
100 mg tablet administered orally, twice a day (BID) on Days 1-5 and Days 8-28 of Cycle 1 (28-day Cycle) and Days 1-21 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Days 1-21 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Name: INCB024360

Biological: pembrolizumab 200 mg
Administered as an intravenous (IV) infusion on Day 8 of Cycle 1 (28 days) and Day 1 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Day 1 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Epacad+Pembro+Cisplatin+Pemetrexed

For each 21-day cycle, participants will receive a one-time IV infusion of 200 mg pembrolizumab on Day 1 and 100 mg of epacadostat orally BID on Days 1-21 for a maximum of 35 cycles. Participants will also receive a one-time IV infusion of 75 mg/m^2 Cisplatin and 500 mg/m^2 Pemetrexed on Day 1 for the first 4 cycles.

With protocol amendment 02, treatment with epcadostat stopped, and participants continued treatment with pembrolizumab, cisplatin and pemetrexed.

Drug: Epacadostat 100 mg
100 mg tablet administered orally, twice a day (BID) on Days 1-5 and Days 8-28 of Cycle 1 (28-day Cycle) and Days 1-21 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Days 1-21 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Name: INCB024360

Biological: pembrolizumab 200 mg
Administered as an intravenous (IV) infusion on Day 8 of Cycle 1 (28 days) and Day 1 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Day 1 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Cisplatin 75 mg/m^2
Administered as an IV infusion on Day 1 of Cycles 1 through 4
Other Names:
  • Platinol®
  • Platinol-AQ®

Drug: Pemetrexed 500 mg/m^2
Administered as an IV infusion on Day 1 of Cycles 1 through 4
Other Name: Alimta®

Experimental: Epacad+Pembro+Carboplatin+Pemetrexed

For each 21-day cycle, participants will receive a one-time IV infusion of 200 mg pembrolizumab on Day 1 and 100 mg of epacadostat orally BID on Days 1-21 for a maximum of 35 cycles. Participants will also receive a one-time IV infusion of Area Under the Curve (AUC) 5 Carboplatin and 500 mg/m^2 Pemetrexed on Day 1 for the first 4 cycles.

With protocol amendment 02, treatment with epcadostat stopped, and participants continued treatment with pembrolizumab, carboplatin and pemetrexed.

Drug: Epacadostat 100 mg
100 mg tablet administered orally, twice a day (BID) on Days 1-5 and Days 8-28 of Cycle 1 (28-day Cycle) and Days 1-21 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Days 1-21 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Name: INCB024360

Biological: pembrolizumab 200 mg
Administered as an intravenous (IV) infusion on Day 8 of Cycle 1 (28 days) and Day 1 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Day 1 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Carboplatin Area Under the Curve (AUC)5
Administered as an IV infusion on Day 1 of Cycles 1 through 4
Other Name: Paraplatin®

Drug: Pemetrexed 500 mg/m^2
Administered as an IV infusion on Day 1 of Cycles 1 through 4
Other Name: Alimta®

Experimental: Epacad+Pembro+Carboplatin+Paclitaxel

For each 21-day cycle, participants will receive a one-time IV infusion of 200 mg pembrolizumab on Day 1 and 100 mg of epacadostat orally BID on Days 1-21 for a maximum of 35 cycles. Participants will also receive a one-time IV infusion of AUC6 Carboplatin and 200 mg/m^2 Paclitaxel on Day 1 for the first 4 cycles.

With protocol amendment 02, treatment with epcadostat stopped, and participants continued treatment with pembrolizumab, carboplatin and paclitaxel.

Drug: Epacadostat 100 mg
100 mg tablet administered orally, twice a day (BID) on Days 1-5 and Days 8-28 of Cycle 1 (28-day Cycle) and Days 1-21 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Days 1-21 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Name: INCB024360

Biological: pembrolizumab 200 mg
Administered as an intravenous (IV) infusion on Day 8 of Cycle 1 (28 days) and Day 1 of Cycles 2 through 35 (21-day Cycles) for the "Epacadostat (Epacad)" study arm and on Day 1 of Cycles 1 through 35 (21-day Cycles) for the "Epacad+Pembrolizumab (Pembro)", "Epacad+Pembro+Cisplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Pemetrexed", "Epacad+Pembro+Carboplatin+Paclitaxel" study arms.
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Paclitaxel 200 mg/m^2
Administered as an IV infusion on Day 1 of Cycles 1 through 4
Other Names:
  • Taxol®
  • Abraxane®
  • Onxol®

Drug: Carboplatin AUC6
Administered as an IV infusion on Day 1 of Cycles 1 through 4
Other Name: Paraplatin®




Primary Outcome Measures :
  1. Number of Participants Experiencing Dose-limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (from first dose up to 28 days) ]
  2. Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: From time of first dose until the end of follow-up (up to 27 months) ]
  3. Number of Participants Discontinuing Study Drug Due to an AE [ Time Frame: From time of first dose until the end of follow-up (up to 24 months) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For Part A: Has a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist.
  • For Part B: Has a histologically-confirmed or cytologically confirmed diagnosis of non-small cell lung carcinoma (NSCLC) stage IIIB/IV, be naïve to systemic therapy, and have confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated. Cohort 1 and 2 must have a histological or cytological diagnosis of non-squamous cancer.
  • Has at least one measurable lesion by computed tomography or magnetic resonance imaging per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • Has Eastern Cooperative Oncology Group(ECOG) Performance Status of 0 or 1
  • Has a life expectancy of ≥3 months
  • Females must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours of study start)
  • Women of childbearing potential and male participants must agree to use adequate contraception during the study through 120 days after the last dose of study medication
  • For Part A: Has provided tissue for programmed cell death ligand 1 (PD-L1)/ Indoleamine 2,3-dioxygenase 1 (IDO1) expression evaluation from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. For Part B submission of tissue is optional.

Exclusion Criteria:

  • Has received prior therapy with an anti-Programmed cell death protein (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agents (including ipilimumab or any other antibody/drug specifically targeting T-cell co-stimulation or checkpoint pathways), or IDO1 inhibitor
  • Is currently participating or has participated in a study with an investigational compound or device within 4 weeks, or 5 times half-life of the investigational compound, whichever is longer, of initial dosing on this study
  • For Part A: Has had chemotherapy, targeted small molecule therapy, radiotherapy, major surgery, or biological cancer therapy (including monoclonal antibodies) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the first dose of study medication, or who has not recovered (≤ Grade 1 or baseline) from adverse events due to a previously administered treatment
  • For Part B: Has received radiotherapy within 7 days of the first dose of trial treatment or radiation therapy to the lung that is > 30 Gray (Gy) within 6 months of the first dose of study medication
  • Is expected to require any other form of systemic or localized anti-neoplastic therapy while in study
  • Has active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has symptomatic ascites or pleural effusion
  • Has an active autoimmune disease that has required systemic treatment
  • Is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 1 week prior to the first dose of study medication
  • Has an active infection requiring systemic therapy
  • Has history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease
  • Has received a live vaccine within 4 weeks prior to the first dose of study medication
  • Has a known hypersensitivity to the components of the trial treatment or another monoclonal antibody
  • For Part B: Has a known sensitivity to any component of cisplatin, carboplatin, paclitaxel or pemetrexed.
  • For Part B: Is on chronic systemic steroids with the exception of use of bronchodilators, inhaled steroids, or local steroid injections
  • For Part B cohort 1 and 2: Is unable to interrupt aspirin or other nonsteroidal ant-inflammatory drugs (NSAIDs), other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
  • For Part B cohort 1 and 2: Is unable or unwilling to take folic acid or vitamin B12 supplementation
  • Is Human Immunodeficiency Virus (HIV)-positive (HIV 1/2 antibodies)
  • Has known history of or is positive for active Hepatitis B (Hepatitis B surface antigen reactive) or has active Hepatitis C (Hepatitis C virus ribonucleic acid)
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children during the study through 120 days after the last dose of study medication
  • Has received monoamine oxidase inhibitors (MAOIs) within the 3 weeks before the first dose of study medication
  • Has any history of Serotonin Syndrome after receiving serotonergic drugs
  • Has presence of a gastrointestinal condition that may affect drug absorption

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02862457


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02862457    
Other Study ID Numbers: 3475-434
MK-3475-434 ( Other Identifier: Merck Protocol Number )
163423 ( Registry Identifier: JAPIC-CTI )
First Posted: August 11, 2016    Key Record Dates
Last Update Posted: February 2, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Advanced Solid Tumors
PD-1
PD1
Programmed Cell Death-1
Programmed Cell Death 1
Programmed Cell Death-Ligand 1 (PD-L1)
Programmed Cell Death-Ligand 2 (PD-L2)
PDL1
PDL2
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Cisplatin
Carboplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors