Patient case: 57-year-old male with lung cancer; genetic feature: FGFR1

Clinical trial: Azacitidine Combined With Pembrolizumab and Epacadostat in Subjects With Advanced Solid Tumors (ECHO-206)

Summary: This is an open-label, Phase 1/2 study in subjects with advanced or metastatic solid tumors. The study will be divided into 2 parts (Part 1 and 2). Part 1 is a dose-escalation assessment to evaluate the safety and tolerability of the DNA methyltransferase inhibitor azacitidine in combination with the programmed death receptor-1 (PD-1) inhibitor pembrolizumab and the indoleamine 2,3-dioxygenase (IDO-1) inhibitor epacadostat. Once the recommended doses have been determined, subjects with previously treated NSCLC and microsatellite-stable colorectal cancer (CRC) will be enrolled into expansion cohorts in Part 2.


Eligibility: Inclusion Criteria:
  -  Willingness to provide written informed consent for the study.
  -  Part 1: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (disease progression; subject refusal or intolerance is also allowable).
  -  Part 2: Subjects with histologically or cytologically confirmed NSCLC:
  -  Stage IIIB or metastatic (Stage IV) NSCLC (according to American Joint Committee on Cancer 7th edition guidelines) who have had disease progression after available therapies for advanced or metastatic disease that are known to confer clinical benefit, been intolerant to treatment, or refused standard treatment.
  -  Prior systemic regimens must include previously approved therapies, including a platinum-containing chemotherapy regimen; a tyrosine kinase inhibitor for tumors with driver mutations; and checkpoint inhibitors where approved (except Cohort A1, which must be checkpoint inhibitor-naive).
  -  Must have disease progression on a prior PD-1-pathway targeted agent (Cohort A2) or must be PD-1 pathway-targeted treatment naive (Cohort A1).
  -  Subjects with recurrent (unresectable) or metastatic CRC:
  -  Have histologically confirmed microsatellite stable (MSS) CRC.
  -  Stage IV MSS CRC (according to American Joint Committee on Cancer 7th edition guidelines) who have had disease progression after available therapies for advanced or metastatic disease that are known to confer clinical benefit, been intolerant to treatment, or refused standard treatment.
  -  Prior systemic regimens must include previously approved therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF therapy (if no contraindication); and if KRAS wild type and no contraindication, an anti-epidermal growth factor receptor (EGFR) therapy; and progressed after the last administration of approved therapy.
  -  Has baseline tumor biopsy specimen available or willingness to undergo a pretreatment and on-treatment tumor biopsy to obtain the specimen.
  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  Exclusion Criteria:
  -  Laboratory parameters not within the protocol-defined range.
  -  Receipt of anticancer medications or investigational drugs within a defined interval before the first administration of study drug.
  -  Has not recovered from toxic effects of prior therapy to ≤ Grade 1.
  -  Active or inactive autoimmune disease or syndrome.
  -  Active infection requiring systemic therapy.
  -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  -  History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful.
  -  Has received a live vaccine within 30 days of planned start of study therapy.
  -  Prior receipt of an IDO inhibitor.

Relevance to patient case: not relevant