First-line treatment of metastatic NSCLC MedDRA version: 20.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration uni
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have a histologically or cytologically confirmed diagnosis of stage IV (AJCC version 8 or current version as applicable) NSCLC. 2. Have confirmation that EGFR, ALK, or ROS1 directed therapy is not indicated as primary therapy (documentation of absence of tumor activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a KRAS mutation). a. If participant’s tumor is known to have a predominantly squamous histology, molecular testing for EGFR mutation and ALK and ROS1 translocations will not be required, as this is not part of current diagnostic guidelines. 3. Have measurable disease based on RECIST 1.1 as determined by the local site. a. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 4. Be =18 years of age on the day of signing informed consent. 5. Have a life expectancy of at least 3 months. 6. Have an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization. 7. A male participant must agree to use contraception as detailed in Appendix 2 of this protocol during the treatment period and for at least 120 days after the last dose of pembrolizumab and epacadostat/matching placebo and up to 180 days after last dose of chemotherapeutic agents. 8. A female participant is eligible to participate if she is not pregnant (see Appendix 2 of the protocol), not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days after the last dose of pembrolizumab and epacadostat/matching placebo and up to 180 days after last dose of chemotherapeutic agents. 9. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. 10. Have adequate organ function as indicated by the laboratory values as defined in the protocol Specimens must be collected and reviewed within 10 days prior to the start of study treatment. 11. Have provided an evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (that was not previously irradiated) for central PD-L1 testing. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 531 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 531
Exclusion criteria
Exclusion criteria: 1. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days before first dose of study treatment 2. Has a history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease 3. Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible 4. Has a 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 5. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). 6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment 7. Has had an allogeneic tissue/solid organ transplant 8. Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority 9. Has known history of or is positive for active Hepatitis B (HBsAg reactive) or has active Hepatitis C (HCV RNA) 10. Has a history of a gastrointestinal condition or procedure that in the opinion of the Investigator may affect oral drug absorption 11. Has a history or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful. Screening QTc interval >480 msec is excluded (corrected by Fridericia or Bazett formula) 12. Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted 13. Has a known history of active tuberculosis (TB; Bacillus tuberculosis). 14. Has an active infection requiring systemic therapy 15. Has known psychiatric or substance abuse disorders that would interfere with the participant’s cooperation for the requirements of the study 16. Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of epacadostat, pembrolizumab, or as applicable, carboplatin, cisplatin, paclitaxel, or pemetrexed 17. WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required 18. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and epacadostat/matching placebo and up to 180 days after last dose of chemotherapeutic agents 19. Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC 20. Has received prior treatment with pembrolizumab or any other anti-PD-1, anti-PD-L1, anti-PD-L2 agent, with epacadostat or any anti-IDO1 agent, or with a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare overall survival (OS) of the combinations of epacadostat + pembrolizumab AND epacadostat + pembrolizumab + chemotherapy versus placebo + pembrolizumab + chemotherapy. 2. To compare progression-free survival (PFS) of the combinations of epacadostat + pembrolizumab AND epacadostat + pembrolizumab + chemotherapy versus placebo + pembrolizumab + chemotherapy.;Secondary Objective: 1. To compare objective response rate (ORR) of the combinations of epacadostat + pembrolizumab AND epacadostat + pembrolizumab + chemotherapy versus placebo + pembrolizumab + chemotherapy. 2. To evaluate duration of response (DOR) of the combinations of epacadostat + pembrolizumab, epacadostat + pembrolizumab + chemotherapy, and placebo + pembrolizumab + chemotherapy. 3. To evaluate the safety and tolerability of the combinations of epacadostat + pembrolizumab, epacadostat + pembrolizumab + chemotherapy, and placebo + pembrolizumab + chemotherapy. 4. To evaluate the pharmacokinetics (PK) of epacadostat.;Primary end point(s): • Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) based on blinded independent central review (BICR). • Overall survival (OS).;Timepoint(s) of evaluation of this end point: • PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. • OS is defined as the time from randomization to death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Objective response rate (ORR) per RECIST 1.1 based on BICR. • Duration of response (DOR) per RECIST 1.1 based on BICR. • Pharmacokinetics of epacadostat • Safety and tolerability;Timepoint(s) of evaluation of this end point: • ORR is defined as the proportion of participants who have a confirmed CR or PR per RECIST 1.1 based on BICR. •DOR defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first, per RECIST 1.1 based on BICR. • Number of participants experiencing AEs and number of participants discontinuing study drug due to AEs. | — |
Countries
Australia, Brazil, Canada, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Russian Federation, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed