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.
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 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 10
unstained sections (5 micron). 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 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 4 weeks prior to registration
- Radiation therapy within 2 weeks 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 5 half-lives, or 5 days, whichever is longer, prior to registration
- 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
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
