Metastatic NSCLC with high PD-L1 expression MedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV 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. Tumor tissue that demonstrates PD-L1 expression in =50% of tumor cells (TPS =50%) as assessed by IHC at a central laboratory a. Assessment of PD-L1 expression must be made from provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin-embedded tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue 5. Be =18 years of age on the day of signing informed consent 6. Have a life expectancy of at least 3 months 7. Have an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization 8. A male participant must agree to use contraception as detailed in the protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period 9. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) OR b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment 10. The participant (or legally acceptable representative if applicable) provides written informed consent for the study 11. Have adequate organ function as indicated by the laboratory values in the protocol. 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 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 68
Exclusion criteria
Exclusion criteria: 1. Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. 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 (including therapeutic thoraco- or paracentesis) 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. Replacement therapy is allowed. 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). In the event that a single QTc is >480 msec, the participant may enroll if the average QTc for 3 ECGs is 30 Gy within 6 mon
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To compare objective response rate (ORR) of the combination of pembrolizumab plus epacadostat versus pembrolizumab plus placebo. ;Secondary Objective: - To compare progression-free survival (PFS) of the combination of pembrolizumab plus epacadostat versus pembrolizumab plus placebo. -To compare overall survival (OS) of pembrolizumab plus epacadostat versus pembrolizumab plus placebo. - To evaluate duration of response (DOR) of the combinations of pembrolizumab plus epacadostat and pembrolizumab plus placebo. - To evaluate the safety and tolerability of the combinations of pembrolizumab plus epacadostat and pembrolizumab plus placebo. ;Primary end point(s): Original protocol - Objective response rate (ORR), is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on blinded independent central review (BICR). Under amendment 5 the study will stop collecting efficacy endpoints.;Timepoint(s) of evaluation of this end point: Original protocol - Objective Response Rate: imaging (CT and/or MRI) every 9 weeks through 54 weeks then every 12 weeks until disease progression or starting a new therapy Under amendment 5 the timing of imaging during the treatment phase is according to the site’s SOC for tumor assessment until PD or initiation of a new anticancer regimen. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Original protocol - PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurs first. -OS is defined as the time from randomization to death due to any cause. - Duration of response (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. - Safety and tolerability: Number of participants experiencing AEs and number of participants discontinuing study drug due to AEs. Under amendment 5 the study will stop collecting efficacy endpoints.;Timepoint(s) of evaluation of this end point: Original protocol - PFS: imaging (CT and/or MRI) every 9 weeks through 54 weeks then every 12 weeks until PD or starting a new therapy - OS: telephone contacts every 3 mo after PD or starting a new therapy. Additional updated survival status may be requested by the Sponsor. - Duration of Response: imaging every 9 weeks through 54 weeks then every 12 weeks until PD or starting a new therapy - Safety: AE/SAE from Screening through 30/90 days after the last dose. AEs assessed at every visit (every 3 weeks) Under amendment 5 the timing of imaging during the treatment phase is according to the site’s SOC for tumor assessment until PD or initiation of a new anticancer regimen. The last study visit is the Safety Follow-up Visit and there will be no follow-up for survival status. | — |
Countries
Australia, Brazil, Canada, Denmark, Estonia, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, New Zealand, Poland, Romania, Russian Federation, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States
Outcome results
None listed