Patient case: 50-year-old female with Lung cancer. Genetic variant: EGFR (L858R). Other conditions: Lupus.

Clinical trial: Study For Patients With NSCLC EGFR Mutations (Del 19 or L858R +/- T790M)

Summary: Phase 1: The Phase 1 study is an open label, multi center, multiple dose, non randomized, safety, pharmacokinetic, and pharmacodynamics dose escalation study of PF 06747775 as a single agent in patients with advanced EGFRm NSCLC (del19 or L858R, +/ -T790M).
  Phase 2: an open label, multi-center, single arm study of PF-06747775 for the assessment of anti-tumor activity in patients with advanced EGFRm (del19 or L858R) advanced NSCLC with T790M (del 19 and T790M or L858R and T790M) and further pharmacokinetic characterization.

Detailed description: Reason for Protocol: Treatment: protocol designed to evaluate one or more interventions for treating a disease, syndrome or condition.

Eligibility: Inclusion criteria (partial list):
  -  Evidence of histologically or cytologically confirmed diagnosis of locally advanced or metastatic EGFRm (del19 or L858R) NSCLC that has progressed after at least 1 prior line of therapy.
  Patients must have at least on measurable lesion as defined by RECIST V1.1 that has not been previously irradiated
  -  Patients must have had disease progression on treatment with an approved EGFR TKI.
  -  In Phase 1, patients may have also received other lines of therapy before or after the EGFR TKI.
  -  In Phase 2, while patients may have had multiple lines of therapy, the last therapy prior to study treatment must have been an approved EGFR TKI and received within 6 weeks prior to study registration.
  -  In the Phase 1 portion:
  -  In the dose escalation and MTD expansion portions patients must be T790M positive or unknown status.
  -  In the PK sub-studies, patients with EGFRm (del 19 or L858R) with any T790M status are eligible to enroll.
  -  In the Phase 2 portion:
  • Patients must have EGFRm (del 19 and T790M or L858R and T790M) NSCLC tumors
  -  Patients must have at least one measurable lesion as defined by RECIST version 1.1
  -  Tumor tissue available (ie, formalin fixed paraffin embedded (FFPE) block or 15 unstained sections (5 micron). If lesser amount of tissue is available, contact the sponsor. An archival specimen is acceptable for Phase 1; a de novo specimen is required for Phase 2.
  -  Patients must have adequate bone marrow, hepatic and renal functions
  -  Negative serum pregnancy test
  Exclusion Criteria (partial list)
  -  Previously diagnosed brain metastases, unless the patient has completed their treatment that is clinically indicated, if any, and has recovered from the acute effects of radiation therapy or surgery prior to study registration, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable.
  -  Major surgery within 2 weeks prior to registration
  -  Radiation therapy, excluding steriotactic radiosurgery, within 1 week prior to registration.
  -  Systemic anti cancer therapy within 2 weeks or 5 half-lives (whichever is longer) of registration excluding EGFR TKIs. Patients on EGFR TKIs must discontinue the agent for a minimum of :
  -  2 days prior to registration for erlotinib or afatinib, or 3 days for gefitinib if they will be part of the lead-in single dose PF-06747775 PK study (Phase 1 Dose Escalation Single and Multiple dose PK and ECG Assessments; Phase 1 Sildenafil at MTD and Japan PK sub-studies). Please contact the Sponsor for direction for any other EGFR TKI.
  -  5 half-lives or 5 days (whichever is longer) prior to registration if they will be starting on continuous PF-06747775 dosing directly (Phase 1 PK sub-studies at RP2D except Japan).
  -  Concurrent use of drugs that are strong P-glycoprotein (P-gp) inhibitors (such as but not limited to: dronedarone, erythromycin, indinavir, indinavir/ritonavir, itraconazole, ketoconazole, lapatinib, lopinavir/ritonavir, quinidine, rifampin, ritonavir, valspodar, verapamil, vorapaxar). Patients must avoid the use of drugs that are known strong P-gp inhibitors for the duration of the study. therapy with a T790M directed agent

Relevance to patient case: definitely relevant