A Study of Pembrolizumab Plus Epacadostat With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-715-06/ECHO-306-06)

• ClinicalTrials.gov Identifier: NCT03322566
• Recruitment Status: Completed
• First Posted: October 26, 2017
• Results First Posted: January 29, 2020
• Last Update Posted: January 24, 2022
• Sponsor: Incyte Corporation
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: October 24, 2017
• First Posted Date: October 26, 2017
• Results First Submitted Date: December 10, 2019
• Results First Posted Date: January 29, 2020
• Last Update Posted Date: January 24, 2022
• Actual Study Start Date: January 9, 2018
• Actual Primary Completion Date: December 13, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2022)

Objective Response Rate (ORR) of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo [ Time Frame: Assessed every 12 weeks up to 24 months ]

ORR is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) based on blinded independent central review (BICR).

Original Primary Outcome Measures (submitted: October 24, 2017)

• Overall survival of epacadostat + pembrolizumab AND epacadostat + pembrolizumab + chemotherapy versus placebo + pembrolizumab + chemotherapy [ Time Frame: Up to 60 months ]
  Defined as the time from randomization to death due to any cause.
• Progression-free survival of epacadostat + pembrolizumab AND epacadostat + pembrolizumab + chemotherapy versus placebo + pembrolizumab + chemotherapy [ Time Frame: Approximately 24 months ]
  Defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first.

Current Secondary Outcome Measures (submitted: January 19, 2022)

• Progression-free Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo [ Time Frame: Up to 24 months ]
  Defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first.
• Overall Survival of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo [ Time Frame: Up to 24 months ]
  Defined as the time from randomization to death due to any cause.
• Duration of Response of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo [ Time Frame: Up to 24 months ]
  Defined as the time from the earliest date of qualifying response until earliest date of disease progression, per RECIST v1.1, or death from any cause, whichever comes first.
• Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 25 months ]
  An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
• Safety and Tolerability of Pembrolizumab + Chemotherapy + Epacadostat Versus Pembrolizumab + Chemotherapy + Placebo as Measured by the Number of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to 25 months ]
  An AE is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of any study drug, whether or not considered related to the study drug.

Original Secondary Outcome Measures (submitted: October 24, 2017)

• Objective response rate of epacadostat + pembrolizumab AND epacadostat + pembrolizumab + chemotherapy versus placebo + pembrolizumab + chemotherapy. [ Time Frame: Approximately 24 months ]
  Defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1
• Duration of response of epacadostat + pembrolizumab, epacadostat + pembrolizumab + chemotherapy, and placebo + pembrolizumab + chemotherapy. [ Time Frame: Approximately 24 months ]
  Defined as the time from the earliest date of qualifying response until earliest date of disease progression, per RECIST v1.1, or death from any cause, whichever comes first.
• Safety and tolerability of epacadostat + pembrolizumab, epacadostat + pembrolizumab + chemotherapy, and placebo + pembrolizumab + chemotherapy as measured by the number of participants experiencing adverse events (AEs). [ Time Frame: Up to 37 months ]
  An 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.
• Safety and tolerability of epacadostat + pembrolizumab, epacadostat + pembrolizumab + chemotherapy, and placebo + pembrolizumab + chemotherapy as measured by the number of participants discontinuing study drug due to AEs. [ Time Frame: Up to 37 months ]
  An 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Pembrolizumab Plus Epacadostat With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo in Metastatic Non-Small Cell Lung Cancer (KEYNOTE-715-06/ECHO-306-06)
• Official Title: A Randomized Phase 2 Study of the Combination of Pembrolizumab (MK-3475) Plus Epacadostat (INCB024360) With Platinum-based Chemotherapy Versus Pembrolizumab Plus Platinum-based Chemotherapy Plus Placebo as First-Line Treatment in Patients With Metastatic Non-Small Cell Lung Cancer
• Brief Summary: The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat with platinum-based chemotherapy versus pembrolizumab plus platinum-based chemotherapy plus placebo as first-line therapy in participants with metastatic non-small cell lung cancer (NSCLC).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Lung Cancer

Intervention

• Drug: Pembrolizumab
  Pembrolizumab administered intravenously every 3 weeks.
  Other Name: MK-3475
• Drug: Epacadostat
  Epacadostat administered orally twice daily.
  Other Name: INCB024360
• Drug: Platinum-based chemotherapy
  Investigator selected one of the following regimens: pemetrexed + cisplatin, pemetrexed + carboplatin, or paclitaxel + carboplatin, depending on histology.
• Drug: Placebo
  Matching placebo administered orally twice daily.

Study Arms

• Experimental: Pembrolizumab + Chemotherapy + Epacadostat
  Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Epacadostat
  • Drug: Platinum-based chemotherapy
• Experimental: Pembrolizumab + Chemotherapy + Placebo
  Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m^2 IV infusion, Q3W + cisplatin 75 mg/m^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles).
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Platinum-based chemotherapy
  • Drug: Placebo
• Experimental: Pembrolizumab + Epacadostat
  Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, BID in each 21 day cycle for up to 35 cycles.
  Interventions:

  • Drug: Pembrolizumab
  • Drug: Epacadostat

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 10, 2018): 233
• Original Estimated Enrollment (submitted: October 24, 2017): 1062
• Actual Study Completion Date: October 16, 2020
• Actual Primary Completion Date: December 13, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of stage IV NSCLC without epidermal growth factor receptor (EGFR)-sensitizing mutation, ROS1 and/or anaplastic lymphoma kinase (ALK) translocation
• Measurable disease based on RECIST 1.1
• Life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function per protocol-defined criteria.
• Provide tumor tissue sample.

Exclusion Criteria:

• Known untreated central nervous system metastases and/or carcinomatous meningitis
• History of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
• Symptomatic ascites or pleural effusion.
• Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
• Active autoimmune disease that has required systemic treatment in past 2 years.
• Has had an allogeneic tissue/solid organ transplant.
• Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
• Has known history of or is positive for active Hepatitis B (HBsAg reactive) or has active Hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
• History or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful.
• Use of protocol-defined prior/concomitant therapy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Hungary, Ireland, Israel, Italy, Korea, Republic of, Mexico, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Brazil, France, Germany, Ukraine

Administrative Information

• NCT Number: NCT03322566
• Other Study ID Numbers: KEYNOTE-715-06/ECHO-306-06; 2017-001810-27 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Lance Leopold, MD; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: January 2022