Phase 3 Study of Pembrolizumab ± Epacadostat in PD-L1 High Metastatic NSCLC

Phase 1

• Conditions: Metastatic NSCLC with high PD-L1 expression; MedDRA version: 20.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001841-28-ES
• Lead Sponsor: Incyte Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-12-01
• Study Completion: 2020-11-09
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 154

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 320
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 268

Exclusion Criteria

1. Has known active 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 not considered systemic treatment.
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 <480 msec.
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 or pembrolizumab.
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 study treatment.
19. Has received prior systemic chemotherapy or other targeted or biological anti-neoplastic 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 an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137, GITR).
21. Has received radiotherapy within 14 days before the first dose of study treatment or received lung radiation therapy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified